Asunto(s)
Amiloidosis , Artritis Reumatoide , Enfermedades Renales , Riñón , Proteína Amiloide A Sérica/metabolismo , Amiloidosis/economía , Amiloidosis/metabolismo , Amiloidosis/patología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Femenino , Humanos , Riñón/lesiones , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/etiología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Masculino , Persona de Mediana EdadRESUMEN
A main feature of Fabry disease is nephropathy, with polyuria an early manifestation; however, the mechanism that underlies polyuria and affected tubules is unknown. To increase globotriaosylceramide (Gb3) levels, we previously crossbred asymptomatic Glatm mice with transgenic mice that expressed human Gb3 synthase (A4GALT) and generated the GlatmTg(CAG-A4GALT) symptomatic Fabry model mice. Additional analyses revealed that these mice exhibit polyuria and renal dysfunction without remarkable glomerular damage. In the present study, we investigated the mechanism of polyuria and renal dysfunction in these mice. Gb3 accumulation was mostly detected in the medulla; medullary thick ascending limbs (mTALs) were the most vacuolated tubules. mTAL cells contained lamellar bodies and had lost their characteristic structure ( i.e., extensive infolding and numerous elongated mitochondria). Decreased expression of the major molecules-Na+-K+-ATPase, uromodulin, and Na+-K+-2Cl- cotransporter-that are involved in Na+ reabsorption in mTALs and the associated loss of urine-concentrating ability resulted in progressive water- and salt-loss phenotypes. GlatmTg(CAG-A4GALT) mice exhibited fibrosis around mTALs and renal dysfunction. These and other features were consistent with pathologic findings in patients with Fabry disease. Results demonstrate that mTAL dysfunction causes polyuria and renal impairment and contributes to the pathophysiology of Fabry nephropathy.-Maruyama, H., Taguchi, A., Nishikawa, Y., Guili, C., Mikame, M., Nameta, M., Yamaguchi, Y., Ueno, M., Imai, N., Ito, Y., Nakagawa, T., Narita, I., Ishii, S. Medullary thick ascending limb impairment in the GlatmTg(CAG-A4GALT) Fabry model mice.
Asunto(s)
Enfermedad de Fabry/patología , Enfermedades Renales/patología , Médula Renal/patología , Animales , Modelos Animales de Enfermedad , Enfermedad de Fabry/metabolismo , Capacidad de Concentración Renal/fisiología , Enfermedades Renales/metabolismo , Médula Renal/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Poliuria/metabolismo , Poliuria/patología , Sodio/metabolismo , Simportadores de Cloruro de Sodio-Potasio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Trihexosilceramidas/metabolismoRESUMEN
The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues. A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens. In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log10%amyloid). The results of sex-, age-, and Log10%amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and the deposition pattern in the glomerulus was nodular. Nodular deposition in extraglomerular mesangium leads to renal impairment in AA group. There are significant differences between AA and AL amyloidosis with regard to the renal function, especially in terms of Ccr, eGFR and urinary protein, even after Log10%amyloid was adjusted; showing that these inter-group differences in renal function would not be depend on the amount of renal amyloid deposits. These differences could be explained by the difference in distribution and morphological pattern of amyloid deposition in the renal tissue.
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Presión Sanguínea , Tasa de Filtración Glomerular , Riñón , Proteinuria , Fiebre Reumática , Proteína Amiloide A Sérica , Anciano , Biopsia , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/fisiopatología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/orina , Riñón/metabolismo , Riñón/patología , Riñón/fisiopatología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Proteinuria/complicaciones , Proteinuria/patología , Proteinuria/fisiopatología , Proteinuria/orina , Fiebre Reumática/complicaciones , Fiebre Reumática/patología , Fiebre Reumática/fisiopatología , Fiebre Reumática/orina , Proteína Amiloide A Sérica/metabolismoAsunto(s)
Amiloide/metabolismo , Amiloidosis/metabolismo , Enfermedades Renales/metabolismo , Amiloidosis/patología , Biopsia , Creatinina/metabolismo , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/metabolismo , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Enfermedades Renales/patología , Modelos LinealesRESUMEN
We detected an increase in small arterioles around glomeruli, particularly adjacent to tuft adhesive lesions in immunoglobulin A nephropathy (IgAN), for the 1 st time, as far as we know. We labeled these as periglomerular microarterioles (PGMAs). This study aimed to clarify the pathological significance of PGMAs. Sixty-two patients with IgAN and 19 controls with minor glomerular abnormalities without proteinuria were evaluated in this study. The number of PGMAs located between the Bowman's capsule and the adjoining tubules was counted for each glomerulus. The mean number of PGMAs per glomerulus in cases of IgAN was significantly higher than those of the controls (0.530 ± 0.477 vs. 0.240 ± 0.182, P <0.05). Serial sections showed that most of the PGMAs were in contact with adjacent glomeruli (71.8%), through tuft adhesive lesions (52.1%), or the vascular pole (19.7%). By single regression analysis, the number of PGMAs was found to be positively correlated with the incidence of glomerular tuft adhesion, glomerular sclerosis, or the area of interstitial fibrosis in IgAN. By multiple regression analysis, the incidence of glomerular tuft adhesion was found to be the only independent pathological feature to correlate with the number of PGMAs (P = 0.0006). We have noticed the existence of PGMAs around glomeruli as a pathological finding of IgAN. Furthermore, the number of PGMAs was associated with the incidence of tuft adhesive lesion in glomeruli of IgAN although there was no relationship between the presence of PGMAs and clinical parameters including urinary protein excretion or creatinine clearance in the present study.
Asunto(s)
Glomerulonefritis por IGA , Humanos , Glomérulos Renales , Proteinuria , Análisis de RegresiónRESUMEN
OBJECTIVE: Ultrastructural studies of IgG4-related kidney disease (IgG4-RKD) characterized by tubulointerstitial nephritis (TIN) are limited in previous reports due to the rarity of the condition. In the present report, we performed ultrastructural examinations and assessed the pathogenesis of this disease. PATIENTS: Clinicopathological studies were conducted in eight patients diagnosed with IgG4-RKD. Routine light, immunofluorescence and electron microscopy examinations and immunohistochemical assessments of IgG4 were performed using renal biopsy samples. RESULTS: Hypocomplementemia, positive anti-nuclear antibodies and eosinophilia were confirmed in more than half of the cases. Electron dense deposits (EDDs) were frequently found in the glomeruli and interstitium. The rate of deposition was 62.5% in both mesangial areas and Bowman's capsule. EDDs were frequently detected on the tubular basement membrane (TBM) (87.5% of patients). The interstitium also contained EDDs on collagen fibers in 87.5% of the cases and on basement membrane-like materials in areas of fibrosis in 37.5% of the cases. The creatinine clearance levels were significantly lower in the patients with the latter pattern. Meanwhile, the rate of immunoglobulin and/or complement deposition on the TBM was observed in less than 37.5% of patients, and these findings were not entirely coincident with the cases of EDDs on the TBM. CONCLUSION: EDDs are frequently found in the glomeruli and interstitium in patients with IgG4-RKD; however, immunohistological studies do not provide evidence that IgG4-RKD involves TIN with immune complex nephropathy. The presence of interstitial EDDs may be related to the progression of interstitial fibrosis in the setting of IgG4-RKD.
Asunto(s)
Inmunoglobulina G/metabolismo , Riñón/patología , Nefritis Intersticial/patología , Anciano , Anciano de 80 o más Años , Membrana Basal/patología , Progresión de la Enfermedad , Eosinofilia/inmunología , Técnica del Anticuerpo Fluorescente , Humanos , Glomérulos Renales/patología , Masculino , Nefritis Intersticial/inmunología , Adulto JovenRESUMEN
A 47-year-old Japanese man was admitted to our hospital for evaluation of proteinuria, which was detected when he was 37 years of age. His creatinine clearance levels had fallen to 76.3 mL/min/1.73 m2. A kidney biopsy was conducted, and the patient's low plasma α-galactosidase A levels suggested Fabry disease. After genetic counseling, GLA analysis revealed a novel mutation p.L387P. Interview with the patient revealed that both his younger brother and mother suffered from cardiomyopathy and were undergoing cardiological treatment. They also were positive for proteinuria. About 30 years ago, the patient's cousin (aged 25) was diagnosed with Fabry disease. He underwent hemodialysis for 9 years until his death at 42. At that time, the patient and his brother had not been investigated for Fabry disease so their cousin could not act as a proband for the brothers. Eventually, the patient, his mother, and his brother were put on enzyme replacement therapy with agalsidase beta. As this series of cases shows, medical interviews to collate both medical and family history were essential for the discovery of Fabry disease in these patients. In addition, being a treatable genetic disorder, Fabry disease should be listed in the standard differential diagnoses of systemic and familial diseases, including unknown cause of nephropathy or cardiomyopathy, for early detection of the disorder.
RESUMEN
A 31-year-old woman with proteinuria, hypocomplementemia, rheumatoid factor, and high serum polyclonal IgM concentration was admitted to our hospital for renal biopsy. She had a past history of two renal biopsies. When she was 12 years old, she developed proteinuria, microscopic hematuria, and hypocomplementemia. She was diagnosed as having 'IgM nephropathy' based on minor glomerular abnormalities as determined by light microscopy and IgM and C3 deposition in the mesangial region by immunofluorescence microscopy at the first biopsy. Despite corticosteroid treatment, her proteinuria did not improve and she discontinued regular outpatient checkups. When she was 29 years old and pregnant, she developed preeclampsia and, after delivery, a second renal biopsy was implemented. She was diagnosed as having progressed 'IgM nephropathy' with endotheliosis induced by preeclampsia. She was treated with angiotensin II receptor blocker and her proteinuria diminished; however, 1 year after the delivery, she developed proteinuria again, along with microscopic hematuria and hypocomplementemia. A third renal biopsy was conducted at 31 years of age and she was diagnosed as having membranoproliferative glomerulonephritis (MPGN) type I on the basis of diffuse mesangial proliferation, endocapillary hypercellularity with double contour of the capillary wall, and lobular formation in glomeruli, as determined by light microscopy. Immunofluorescence staining demonstrated deposits of C3, C4, C1q, and IgM in the mesangial region and capillary wall. She underwent corticosteroid therapy followed by normalization of urinalysis and serum complement level. Although she had initially been diagnosed with 'IgM nephropathy', she was finally diagnosed with secondary MPGN and was successfully treated by corticosteroid therapy.
RESUMEN
BACKGROUND: IgG4-related disease is a multi-organ disorder characterized by a high level of serum IgG4 and dense infiltration of IgG4-positive cells into affected organs. In routine studies, however, IgG subclasses are not estimated. In the present study, we attempted to clarify the light-microscopic characteristics of IgG4-related tubulointerstitial nephritis (TIN) to facilitate distinction from non-IgG4-related TIN in specimens obtained by renal biopsy using routine staining. METHODS: In specimens from 34 cases of TIN (13 IgG4-related and 21 non-IgG4-related), 9 nephrologists independently reviewed the following histological features of interstitial lesions: (i) cell infiltration extending into the renal capsule, (ii) cell infiltration into the renal medulla, (iii) regional lesion distribution, (iv) lymphoid follicles, (v) granulomatous lesions, (vi) necrotizing angiitis, (vii) eosinophil infiltration, (viii) neutrophil infiltration, (ix) tubulitis, (x) peritubular capillaritis, (xi) storiform fibrosis and (xii) the stage of interstitial fibrosis. The modified nominal group technique was applied to obtain a consensus in the pathological interpretation. RESULTS: Consensus was successfully attained among the diagnosticians for all but one pathological feature (regional lesion distribution). Storiform fibrosis was demonstrated in 12 of 13 (92.3%) cases of IgG4-related TIN but in none of the cases of other types of TIN. Cell infiltration extending into the renal capsule was also observed only in IgG4-related TIN. Conversely, neutrophil infiltration, severe tubulitis, severe peritubular capillaritis, granulomatous lesions and necrotizing angiitis were evident only in non-IgG4-related TIN. CONCLUSIONS: This study revealed some useful and characteristic features for distinguishing IgG4-related from non-IgG4-related TIN on the basis of light-microscopic observation.
Asunto(s)
Rechazo de Injerto/metabolismo , Inmunoglobulina G/metabolismo , Nefritis Intersticial/metabolismo , Nefritis Intersticial/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Rechazo de Injerto/patología , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Trasplante Homólogo , Adulto JovenRESUMEN
BACKGROUND: Arg95Stop mutation of exon 4 in complement component 9 (C9) gene is common in individuals in Japan with C9 deficiency (C9D); however, understanding of the influences of C9D on human glomerulonephritis remains elusive. METHODS: A total of 1288 patients with chronic kidney disease (CKD) were recruited from the hospitals in Niigata prefecture. They were screened for the Arg95Stop mutation of C9 gene by allele-specific PCR. RESULTS: We identified two individuals with C9D among 1,288 CKD patients, a frequency comparable to that of the general Japanese population (0.16%). Case 1 involved a 44-year-old man presenting with nephrotic proteinuria. The hemolytic activity of CH50 was low, and the concentration of C9 was not detected. Sequencing of exon 4 of the C9 gene showed the Arg95Stop mutation. Renal biopsy revealed diffuse global mesangial proliferation with extensive duplication of glomerular capillary walls. Mesangial, subendothelial and subepithelial deposits were noticed with light and electron microscopy. Immunofluorescent study showed predominant mesangial IgA deposition. Case 2 involved a 62-year-old man presenting with proteinuria and hematuria. His CH50 level was decreased. Renal biopsy revealed diffuse global mesangial proliferation with extensive duplication of glomerular capillary walls. Immune deposits were also confirmed. The percentage of C9D among patients with mesangial proliferation and duplication of GBM in this study was 5.1%. CONCLUSION: These results suggested that the lack of membrane attack complex because of an Arg95Stop mutation of the C9 gene predisposed patients to pathognomonic glomerulonephritis.
Asunto(s)
Arginina/genética , Complemento C9/deficiencia , Complemento C9/genética , Glomerulonefritis/genética , Glomerulonefritis/patología , Mutación , Adulto , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Humanos , Japón , Fallo Renal Crónico/genética , Fallo Renal Crónico/patología , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
A 78-year-old-man was admitted to our hospital because of renal insufficiency 20 months after the onset of autoimmune pancreatitis. He had cerebral infarction and prostatic hypertrophy as complications. He had been previously diagnosed with autoimmune pancreatitis (AIP). The initial therapy was started with oral prednisolone at the dose of 0.8 mg/kg (40 mg/day). Prednisolone had been tapered off gradually through a one-year period. Four months later from terminating prednisolone, a follow-up CT showed multiple low-density areas in both kidneys without swelling of the pancreas. Furthermore, 4 months later, laboratory findings showed progressive renal insufficiency. On admission, BP was 167/77 mmHg, and the bilateral submaxillary glands were swollen. He did not have pretibial edema. Laboratory findings were as follows. BUN 55.9 mg/dL, Cre 6.17 mg/dL, Amy 65 mg/dL, TP/Alb 9.5/4 g/dL, gamma-gl 43.7%, IgG/IgA/IgM 3,395/112/74 mg/dL, IgG4 1,460 mg/dL, urinary protein 1.38 g/day, and 24 hr-Ccr 11.8 mL/min/1.73 m2. Percutaneous renal needle biopsy was conducted. Light microscopic findings demonstrated tubulointerstitial nephritis (TIN) and membranous change. Immunofluorescent microscopic findings indicated diffuse deposition of IgG2 and IgG4 in the renal interstitium. On the basis of these findings, the condition was diagnosed as IgG4-related tubulointerstitial nephritis. As renal insufficiency was progressing, hemodialysis was started soon after admission and oral prednisolone was also started at the dose of 0.4 mg/kg (20 mg/day). However, improvement of renal function has not been obtained and hemodialysis and prednisolone tapering are still being conducted. This case showed severe tubulointerstitial nephritis requiring hemodialysis after a cure for autoimmune pancreatitis. IgG4-related renal disease rarely needs hemodialysis. This case indicates that the prognosis of IgG4-related systemic disease is not necessarily good and further accumulation of cases is required.
Asunto(s)
Enfermedades Autoinmunes/complicaciones , Inmunoglobulina G , Nefritis Intersticial/etiología , Pancreatitis/complicaciones , Insuficiencia Renal/etiología , Anciano , Enfermedades Autoinmunes/tratamiento farmacológico , Progresión de la Enfermedad , Humanos , Masculino , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/inmunología , Nefritis Intersticial/terapia , Pancreatitis/tratamiento farmacológico , Prednisolona/administración & dosificación , Pronóstico , Diálisis Renal , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/terapia , Factores de TiempoRESUMEN
We report a case of a 29-year-old male patient with a generalized adenovirus (AdV) infection after cord blood transplantation (CBT) for acute myelocytic leukemia with maturation at 2nd complete remission. Before engraftment, hemorrhagic cystitis was caused by AdV, which resulted in hydronephrosis, renal failure, and adenoviremia on day 34. Forced diuresis, hemodialysis, withdrawal of cyclosporin A, and administration of gamma-globulin or vidarabine were not effective and the patient died of pulmonary alveolar hemorrhage on day 67. At autopsy, old inflammatory change only was observed in the bladder section. In the lungs and kidneys, granular deposits in the nucleus and a high copy number of AdV-DNA were observed. Molecular diagnosis using PCR-restriction fragment length polymorphism analysis demonstrated that AdV with the serotype 14 caused the cystitis. However, retrospective genome typing using PCR sequencing revealed the infection of AdV serotype 35 in the kidneys, lungs, and serum. The present case suggested that Adv infection could not be always caused by a single AdV serotype, and suggested that multiple serotype infection was very difficult to treat. It is desired that a consensus regarding the treatment of AdV infections is established.
Asunto(s)
Infecciones por Adenovirus Humanos/etiología , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Cistitis/etiología , Hemorragia/etiología , Leucemia Mieloide Aguda/terapia , Adulto , Cistitis/patología , Cistitis/virología , Resultado Fatal , Hemorragia/virología , Humanos , Masculino , Vejiga Urinaria/patologíaRESUMEN
We report here unique electron microscopy findings showing clusters of deposition of spherical and tubular microparticles in a glomerular basement membrane (GBM) of a 46-year-old Japanese male with membranous nephropathy. Another distinct feature was the deep infolding of podocyte membranes into the GBM. Light microscopy showed the ladder formation of the GBM suggesting membranous nephropathy, while the immunofluorescent examination was atypical for the absence of the global capillary deposition of IgG and C3. He had mild liver dysfunction with positive hepatitis B antigen. Antibodies to hepatitis B surface antigen reacted weakly on the GBM in the immunohistochemistry. We suspected the unique findings of this case might be related to the hepatitis B viral infection.
Asunto(s)
Membrana Basal Glomerular/ultraestructura , Glomerulonefritis Membranosa/patología , Hepatitis B/patología , Podocitos/ultraestructura , Membrana Basal Glomerular/patología , Humanos , Masculino , Microesferas , Persona de Mediana Edad , Podocitos/patologíaRESUMEN
BACKGROUND/AIMS: Mutations of the endosomal chloride/proton exchanger gene, CLCN5, cause Dent's disease, an X-linked recessive proximal tubular disorder. The renal endocytic system was found to be affected in clcn5 knockout mice. However, the impaired endocytic machinery of Dent's disease patients has not been thoroughly investigated. METHODS: The CLCN5 gene was sequenced in a Japanese patient with Dent's disease and his family. The loss-of-function phenotype of the missense CLCN5 mutation was investigated by gene expression in Xenopus oocytes and CHO cells. Immunohistochemical analysis was performed on kidney biopsy specimens for endocytic machinery proteins, megalin, cubilin, and disabled-2 (Dab2) in proximal tubules. RESULTS: Genomic analysis revealed a novel G-to-A transition at the first nucleotide of the 333rd codon of CLCN5, causing a substitution of glycine with arginine. Inefficient expression of the mutant gene in Xenopus oocytes resulted in abolished chloride currents. Impaired N-glycosylation of the mutant protein was evident in the DNA-transfected CHO cells. Proximal tubular expression of megalin, cubilin, and Dab2 was markedly reduced and irregular staining in some portions was observed in the patient compared with controls. CONCLUSIONS: A novel G333R CLCN5 mutation caused defective expression of megalin, cubilin, and Dab2 in a patient with Dent's disease.
Asunto(s)
Canales de Cloruro/genética , Enfermedades Renales/genética , Enfermedades Renales/fisiopatología , Túbulos Renales Proximales/fisiopatología , Mutación Missense , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Animales , Proteínas Reguladoras de la Apoptosis , Células CHO , Canales de Cloruro/metabolismo , Cricetinae , Cricetulus , Salud de la Familia , Humanos , Enfermedades Renales/metabolismo , Túbulos Renales Proximales/metabolismo , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Masculino , Oocitos , Linaje , Fenotipo , Receptores de Superficie Celular/metabolismo , Proteínas Supresoras de Tumor , XenopusRESUMEN
OBJECTIVE: Recently, a new concept of IgG4-related systemic disease including autoimmune pancreatitis, characterized by a high serum IgG4 level and tissue infiltration by IgG4-positive plasma cells, has been proposed. Our aim was to investigate the renal involvement in this condition. PATIENTS AND METHODS: We investigated the results of laboratory and imaging studies of the kidneys in 7 patients with IgG4-related systemic disease, and examined the renal histology in four of them. All patients showed elevated serum IgG4 levels, and 4 had autoimmune pancreatitis. The other three patients showed involvement of various extrapancreatic organs (lymphadenopathy, sialadenitis or renal insufficiency), and abundant IgG4-positive plasma cell infiltration was confirmed in their affected tissues. RESULTS: Six of the 7 patients showed some renal abnormalities. In one patient, hydronephrosis was observed accompanied by retroperitoneal fibrosis. Another patient showed multiple low-density areas in both kidneys by computed tomography, and gallium citrate scintigraphy showed gallium-67 accumulation in both kidneys, although renal function was normal. Four patients had tubulointerstitial nephritis. In two of them, the tubulointerstitial nephritis was diffuse. In one patient, marked diffuse but patchily distributed lymphoplasmacytic infiltration of the renal interstitium was observed. In another patient, computed tomography showed a tumor-like low-density mass; open biopsy of the mass showed aggregates of lymphocytes and plasma cells in the renal interstitium. CONCLUSION: Renal parenchymal lesions in IgG4-related systemic disease are due to dense lymphoplasmacytic infiltration of the renal interstitium, and the lesions vary from diffuse tubulointerstitial nephritis to tumor-like masses according to the distribution patterns of the infiltrating cells.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Inmunoglobulina G/sangre , Enfermedades Renales/inmunología , Pancreatitis/inmunología , Anciano , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/complicaciones , Humanos , Riñón/patología , Enfermedades Linfáticas/complicaciones , Enfermedades Linfáticas/inmunología , Masculino , Persona de Mediana Edad , Pancreatitis/sangre , Pancreatitis/complicaciones , Células Plasmáticas/patología , Insuficiencia Renal/complicaciones , Insuficiencia Renal/inmunología , Sialadenitis/complicaciones , Sialadenitis/inmunologíaRESUMEN
We report three patients with tubulointerstitial nephritis (TIN) with high serum IgG4 concentrations. None of the patients had notable pancreatic lesions when the TIN developed, although one had a history of autoimmune pancreatitis (AIP). Nevertheless, the clinicopathological findings were quite similar to those of AIP. They were all middle-aged to elderly men. Sialadenitis and lymphadenopathy were often evident. Serum total IgG and IgG4 concentrations were elevated and hypocomplementemia was observed. Although antinuclear antibodies were positive, anti-Ro and anti-La antibodies were negative. Renal biopsy showed dense lymphoplasmacytic infiltration with fibrosis in the renal interstitium, and the infiltrated plasma cells had strong immunoreactivity for IgG4. Furthermore, lymphoplasmacytic infiltration and abundant IgG4-positive plasma cells were observed in the salivary glands of a patient. Steroid therapy was effective for TIN in all three patients. The present findings support the recently proposed concept of IgG4-related systemic disease, and suggest that IgG4 is associated not only with AIP but also with other systemic lymphoplasmacytic diseases, including TIN. The conditions responsible for the pathogenesis of TIN need to be considered, irrespective of the presence of AIP.
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Inmunoglobulina G/sangre , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/inmunología , Anciano , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Glomerulonefritis Membranoproliferativa/sangre , Glomerulonefritis Membranoproliferativa/inmunología , Humanos , Inmunoglobulina G/fisiología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/sangre , Páncreas/patología , Pancreatitis/inmunología , Pancreatitis/patología , Sialadenitis/sangre , Sialadenitis/inmunologíaRESUMEN
We describe the case of a 44-year-old woman who presented with renovascular hypertension caused by primary leiomyosarcoma of the abdominal aorta that had metastasized into the renal arteries. Despite an extensive radiological evaluation, the diagnosis was mistaken first for Takayasu's arteritis and then for retroperitoneal hematoma or neoplasm. The patient developed renal failure due to bilateral renal infarction, and died 3 months after her initial presentation with ischemic colitis. Postmortem examination confirmed the diagnosis.
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Aorta Abdominal/patología , Hipertensión Renovascular/etiología , Leiomiosarcoma/complicaciones , Neoplasias Vasculares/complicaciones , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Hipertensión Renovascular/diagnóstico , Hipertensión Renovascular/patología , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/patología , Células Neoplásicas Circulantes/patología , Arteria Renal/patología , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/patologíaRESUMEN
Thrombotic thrombocytopenic purpura (TTP) is a rare complication of mixed connective tissue disease (MCTD). In this report, we describe the case of a 73-year-old Japanese woman with MCTD who developed fever, thrombocytopenia, and microangiopathic hemolytic anemia and was diagnosed with MCTD together with TTP. The activity of von Willebrand factor (vWF) cleaving metalloprotease ADAMTS13 was low and considered to have contributed to the disease activity of TTP. The patient died despite intensive treatment of plasma exchange (PEX) and steroid pulse therapy. Autopsy results revealed that the kidneys had platelet and fibrin thrombi, which occluded capillaries and arterioles. These findings were compatible with TTP and the decreased activity of ADAMTS13 was considered to be associated with the disease activity of TTP.
Asunto(s)
Enfermedad Mixta del Tejido Conjuntivo/complicaciones , Púrpura Trombocitopénica Trombótica/complicaciones , Proteínas ADAM/sangre , Proteínas ADAM/deficiencia , Proteína ADAMTS13 , Anciano , Resultado Fatal , Femenino , Humanos , Enfermedad Mixta del Tejido Conjuntivo/sangre , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/sangreRESUMEN
BACKGROUND: It is suggested that IgA nephropathy (IgAN) manifests differently in children vs adults on the basis of biopsy findings. However, this has been difficult to establish owing to the uncertainty of the timing of disease onset in adult IgAN. We addressed this question by comparing both histology and leucocyte accumulation in biopsies of recently diagnosed childhood and adult IgAN. METHODS: Biopsies taken within 2 years from the onset of renal abnormalities in 33 childhood (10 +/- 3 years of age) and 38 adult (35 +/- 6 years) cases of IgAN were examined for histological changes (cellularity in mesangial, endocapillary and extracapillary areas, matrix expansion, adhesions/crescents and interstitial damage), glomerular deposition of immunoglobulin and complement, and the presence of macrophages, activated macrophages and T cells by immunohistochemistry. RESULTS: Glomerular hypercellularity owing to increased cells in mesangial area was prominent in paediatric IgAN and significantly greater than in adult IgAN. In contrast, glomerular matrix expansion, crescent formation and interstitial damage were more severe in adults compared to paediatric IgAN. Indeed, glomerular hypercellularity correlated with proteinuria in paediatric but not in adult IgAN, whereas glomerular matrix correlated with proteinuria and renal function in adult but not in paediatric IgAN. The degree of C3c deposition was significantly greater in paediatric IgAN, while deposition of fibrinogen was greater in adult IgAN. Glomerular and interstitial CD68+ macrophages and a subset of sialoadhesin (Sn)+ activated macrophages were identified in both paediatric and adult IgAN, being significantly greater in number in adult IgAN. Glomerular leucocyte infiltration correlated with proteinuria while interstitial leucocyte infiltration correlated with interstitial damage in both groups. However, only the subset of Sn+ macrophages gave a significant correlation with renal function, glomerular hypercellularity and glomerular matrix. CONCLUSIONS: This study has demonstrated significant differences in the early glomerular lesions of IgAN in children vs adults. Furthermore, Sn+ activated macrophages are implicated in the pathogenesis of IgAN in both patient groups. The prognostic significance of these findings warrants further study.
Asunto(s)
Glomerulonefritis por IGA/patología , Adolescente , Adulto , Factores de Edad , Biopsia , Niño , Preescolar , Femenino , Humanos , Recién Nacido , Masculino , Persona de Mediana EdadRESUMEN
In this report, we describe the case of a 50-year-old Japanese woman with Takayasu arteritis who developed severe proteinuria and renal dysfunction. Abdominal computed tomography did not show narrowing of both renal arteries. Although her levels of C-reactive protein were negative, plasma vascular endothelial growth factor (VEGF) and serum interleukin (IL)-6 levels were elevated. Renal biopsy showed glomerulonephropathy mimicking membranoproliferative glomerulonephritis (MPGN) with glomerular capillary wall thickening (double contour). This was accompanied by mesangial cell proliferation and moderate increase of mesangial matrix without deposits of C3. These findings are quite different from MPGN as electron microscopy did not show subendothelial deposit and circumferential mesangial interposition. Here, we present the case of Takayasu arteritis associated with MPGN-like renal manifestation and elevated VEGF and IL-6. The presence of elevated VEGF and IL-6 could be factors that might contribute to MPGN-like appearance.