COVID-19, glomerulonefritis ANCA y anti-membrana basal glomerular. Caso clínico / Association of COVID-19 and glomerulonephritis with ANCA and anti-glomerular basement membrane antibodies. Report of one case

Renal involvement in COVID-19 infection is varied and worsens its outcome and prognosis. However, the association of COVID-19 infection with glomerulonephritis is exceptional. We report a 46-year-old woman with COVID-19 who had an acute kidney injury and ANCA associated glomerulonephritis two weeks after the onset of the disease. The kidney biopsy showed a crescentic glomerulo-nephritis and the presence of anti-glomerular basement membrane antibodies (GBM-Abs). She was treated with steroids and oral cyclophosphamide with good response without requiring plasmapheresis. Plasma anti GBM-Abs were negative. This case suggests that the presence of anti-GBM-Abs in the kidney, was temporally related to COVID-19 pulmonary damage. The absence of plasma antibodies is probably due to transient production and glomerular adsorption, but with unknown pathogenic role.

Glomerulonefritis C3 en un paciente con síndrome de Alport: un caso raro

El síndrome de Alport es una entidad hereditaria que se produce principalmente por una mutación en los genes que codifican el colágeno tipo IV. Por otro lado, la glomerulonefritis C3 es una entidad rara que presenta un patrón de glomerulonefritis membranoproliferativa y su etiología se basa en un control anormal de la activación de la vía alternativa del complemento. A continuación se describe un caso de un paciente, de sexo masculino, que cursa con un síndrome nefrótico corticorresistente en el que se documenta un patrón de glomerulonefritis membranoproliferativa en la biopsia renal con depósitos de C3 en la inmunofluorescencia, asociada a una deleción heterocigota en el gen CFHR1 en el estudio genético de las proteínas reguladoras del complemento. Además, en el panel genético realizado por corticorresistencia se encuentra una variante COL4A5 asociada al síndrome de Alport ligado al X. Estas entidades pueden presentarse con un curso clínico diverso, pero al estar asociadas pueden acelerar la progresión a enfermedad renal crónica, por lo que se hace necesario hacer un seguimiento clínico más estricto.

Alport Syndrome is a hereditary entity that occurs mainly due to a mutation in the genes that encode type IV collagen. C3 glomerulonephritis is a rare entity with a pattern of membranoproliferative glomerulonephritis and its etiology is based on abnormal control of the activation of the alternative complement pathway. We describe a case of a male patient who presents with a corticosteroid nephrotic syndrome in which a pattern of membranoproliferative glomerulonephritis is documented in the renal biopsy with C3 deposits in the immunofluorescence, associated with a heterozygous deletion in the gene CFHR1 in the genetic study of complement regulatory proteins. Furthermore, a variant COL4A5 associated with X-linked Alport syndrome is found in the genetic panel for corticosteroid resistance. These entities can present with a diverse clinical course, but when associated they can accelerate progression to chronic kidney disease, which is why makes it necessary to do a more strict clinical follow-up.

Analysis of clinical phenotype and genotype of LAMB2 mutation / 中华肾脏病杂志

Objective:To report two cases of steroid-resistant nephrotic syndrome (SRNS) caused by LAMB2 gene mutation, and summarize the characteristics of genotype, clinical and pathological phenotypes of children with LAMB2 gene mutation. Methods:Two cases with SRNS caused by LAMB2 gene mutation were from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in December 2013 and September 2019. The demographic, family history and clinical data of two cases were collected, and the peripheral blood genomic DNA was captured and sequenced by whole exome sequencing. PubMed, Medline, CNKI and Wanfang databases were searched to summarize the clinicopathological phenotypes and genotypes of patients with LAMB2 mutation. Results:Among the two cases with SRNS caused by LAMB2 gene mutation, the clinical phenotypes were all manifested as nephrotic level of proteinuria and hypoalbuminemia, and there was no extrarenal clinical manifestation. One case presented with basement membrane delamination and the other with focal segmental glomerulosclerosis (FSGS). LAMB2 mutations of two cases were Exon32 c.5390G>T(p.Cys1797Phe), Exon19 c.2557C>T(p.Arg853*) and Exon27 c.4370G>A(p.R1457Q), Exon23 c.3325G>A(p.E1109K), respectively. In literature retrieval, there were 37 cases with LAMB2 gene mutation, including 24 cases with renal biopsy data, 13 cases of focal segmental glomerulosclerosis (FSGS), 4 cases of minimal change disease, one case of diffuse mesangial sclerosis, one case of IgM nephropathy, two cases of thin basement membrane nephropathy, and three cases of mesangial hyperplasia. Among them, eight cases had basement membrane delamination tear. Among the 37 cases, 11 cases were homozygous, 22 cases were complex heterozygosity, and 4 cases were heterozygous mutation. Conclusions:LAMB2 mutation may cause delamination tear of glomerular basement membrane. The clinical phenotype is congenital nephrotic syndrome or SRNS. The literature review shows the extrarenal manifestations caused by LAMB2 mutation are mostly various ocular abnormalities, as well as respiratory, digestive and nervous system abnormalities, and the time of progression to end-stage renal disease is also different.

Reporte de un caso de glomerulonefritis rápidamente progresiva por anticuerpos antimembrana basal glomerular / Case report of rapidly progressive glomerulonephritis due to anti-glomerular basement membrane antibodies

RESUMEN Una vez más en medicina interna no podemos, aún, prescindir de los métodos invasivos para alcanzar un diagnóstico. Los avances diarios en el hallazgo de nuevas herramientas paraclínicas no permiten reemplazar aquellos métodos de certeza como la anatomía patológica. El caso presentado es una muestra de ello. Se trata de una mujer de 27 años de edad, con antecedente de tiroiditis de Hashimoto que consulta por presentar severo deterioro de la función renal asociado a oligoanuria. Realizamos una revisión del tratamiento de las glomerulonefritis rápidamente progresivas por anticuerpos antimembrana basal glomerular, serológicamente negativas.

ABSTRACT Once again in internal medicine we cannot do a diagnosis without invasive methods. Daily advances in the finding of new paraclinical tools do not allow the replacement of certain methods such as pathological anatomy. The case presented is a sample of this. This is a 27-year-old woman with a history of Hashimoto's thyroiditis who consults for presenting severe impairment of kidney function associated with oligoanuria. We performed a review of the treatment of the rapidly progressive glomerulonephritis for serologically negative anti-GBM antibodies.

Recurrencia de Síndrome de Goodpasture con negativización de anticuerpos anti-membrana basal glomerular: caso clínico / Recurrence of goodpasture syndrome with negative antiglomerular basement antibodies: report of one case

Goodpasture Syndrome is described as a single episode disease entity. It is diagnosed with the demonstration of antiglomerular basement (anti-GBM) antibodies in plasma or renal tissue. Although the recurrence of anti-GBM disease is rare, it has been reported in up to 3% of cases. Recurrence with negative anti-GBM antibodies in plasma is even less frequent We report a 63 years old male in whom anti-GBM disease recurred without detectable anti-GBM antibodies in plasma, despite having positive antibodies at the onset.

ANCA associated vasculitis: experience of a tertiary care referral center / Vasculite associada a ANCA: experiência de um centro de referência de atendimento terciário

ABSTRACT Background and objectives: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a small vessel vasculitis with insufficient epidemiologic estimates in the United States. We aimed to determine demographic and clinical features of ANCA associated vasculitis patients presenting to a large tertiary care referral center in Upstate New York. Design, setting, participants, and measurements: A retrospective analysis of cases with pauci-immune GN on renal biopsy and clinical diagnosis of ANCA vasculitis presenting over 11 years was conducted. Outcomes of interest were: demographics, ANCA antibody positivity, patient and renal survival, and regional trends. Results: 986 biopsies were reviewed, 41 cases met the criteria for inclusion: 18 GPA, 19 MPA, and 4 double positive (anti-GBM disease plus ANCA vasculitis). Mean age at presentation was 52.4 years (SD 23.7), 23 (56%) were male and median creatinine was 2.6 mg/dL. The median patient follow up was 77 weeks (IQR 10 - 263 weeks), with a 3-month mortality rate of 5.7% and a 1-year estimated mortality rate of 12%. Thirteen patients required hemodialysis at the time of diagnosis; 7 patients came off dialysis, with median time to renal recovery of 4.86 weeks (IQR 1.57 - 23.85 weeks). C-ANCA positivity (p < 0.001) and C-ANCA plus PR3 antibody pairing (p = 0.005) was statistically significant in GPA versus MPA. P-ANCA positivity was observed in MPA versus GPA (p = 0.02) and double positive versus GPA (p = 0.002), with P-ANCA and MPO antibody pairing in MPA versus GPA (p = 0.044). Thirty-seven of the 41 cases were referred locally, 16 cases were from within a 15-mile radius of Albany, Schenectady, and Saratoga counties. Conclusions: ANCA vasculitis is associated with end stage renal disease and increased mortality. Our study suggests the possibility of higher regional incidence of pauci-immune GN in Upstate New York. Further studies should investigate the causes of clustering of cases to specific regions.

RESUMO Introdução e objetivos: A vasculite associada a anticorpos anticitoplasma de neutrófilo (ANCA) é uma vasculite de pequenos vasos com estimativas epidemiológicas insuficientes nos Estados Unidos. Nosso objetivo foi determinar características demográficas e clínicas de pacientes com vasculite associada à ANCA, apresentando-se a um grande centro de referência de atendimento terciário em Upstate New York. Formato, cenário, participantes e medidas: Foi realizada uma análise retrospectiva dos casos de GN pauci-imune em biópsias renais e diagnóstico clínico de vasculite ANCA por mais de 11 anos. Os resultados de interesse foram: dados demográficos, positividade de anticorpos ANCA, sobrevidas renal e de pacientes e tendências regionais. Resultados: 986 biópsias foram revisadas, 41 casos preencheram os critérios de inclusão: 18 GPA, 19 PAM, e 4 duplo-positivos (doença anti-MBG com vasculite ANCA). A média de idade na apresentação foi de 52,4 anos (DP 23,7), 23 (56%) eram do sexo masculino e mediana de creatinina de 2,6 mg/dL. O acompanhamento mediano dos pacientes foi de 77 semanas (IQR 10 - 263 semanas), com uma taxa de mortalidade de 3 meses de 5,7% e uma taxa de mortalidade estimada em 1 ano de 12%. Treze pacientes necessitaram de hemodiálise no momento do diagnóstico; 7 pacientes saíram da diálise, com tempo médio para recuperação renal de 4,86 semanas (IQR 1,57 - 23,85 semanas). A positividade para C-ANCA (p < 0,001) e o pareamento de anticorpos C-ANCA mais PR3 (p = 0,005) foram estatisticamente significantes em GPA versus PAM. A positividade de P-ANCA foi observada em PAM versus GPA (p = 0,02) e duplo positivo versus GPA (p = 0,002), com pareamento de anticorpos P-ANCA e MPO em PAM versus GPA (p = 0,044). Trinta e sete dos 41 casos foram encaminhados localmente, 16 casos foram de dentro de um raio de 15 milhas dos condados de Albany, Schenectady e Saratoga. Conclusões: A vasculite por ANCA está associada à doença renal terminal e aumento da mortalidade. Nosso estudo sugere a possibilidade de maior incidência regional de GN pauci-imune no norte do estado de Nova York. Novos estudos devem investigar as causas do acúmulo de casos em regiões específicas.

Concurrent Anti-glomerular Basement Membrane Nephritis and IgA Nephropathy

Anti–glomerular basement membrane (GBM) nephritis is characterized by circulating anti-GBM antibodies and crescentic glomerulonephritis (GN) with deposition of IgG along the GBM. In a limited number of cases, glomerular immune complexes have been identified in anti-GBM nephritis. A 38-year-old female presented azotemia, hematuria, and proteinuria without any pulmonary symptoms. A renal biopsy showed crescentic GN with linear IgG deposition along the GBM and mesangial IgA deposition. The patient was diagnosed as concurrent anti-GBM nephritis and IgA nephropathy. Therapies with pulse methylprednisolone and cyclophosphamide administration were effective. Concurrent cases of both anti-GBM nephritis and IgA nephropathy are rare among cases of anti-GBM diseases with deposition of immune complexes. This rare case of concurrent anti-GBM nephritis and IgA nephropathy with literature review is noteworthy.

Establishment of rat model of anti-glomerular basement membrane nephritis induced by pCol (24-38) / 解放军医学杂志

Objective Polypeptide pCol (24-38) containing rat non-collagen region of collagen type IV alpha 3 chain [α3(IV)NC1] was used as antigen to establish the rat model of anti-glomerular basement membrane (GBM) disease, and study the possible pathogenesis of anti-GBM disease. Methods Twenty male WKY rats, 8-10 weeks old and weight 120-150g, were randomly divided into control group and anti-GBM model group (10 each). Polypeptide pCol(24-38) was used as antigen in anti-GBM model group, while pCol (38-52) was used as antigen in control group. After emulsification with complete Freund's adjuvant, rats in the both groups were immunized by subcutaneous injection at three points on the back. 24-hour urine was collected regularly every week after immunization to measure the urinary protein content. All animals were sacrificed 49 days after immunization, and serum was taken. The serum creatinine level was detected by creatine oxidase method, urea nitrogen concentration was determined by urease method, and the relative titer of serum anti-pCol (24-38) antibodies was detected by indirect ELISA. Part of kidney tissue was stained with PAS and immunohistochemically treatment in paraffin section, and the other part was frozen section after OCT embedding to detect IgG deposition in glomeruli by direct immunofluorescence method. Results The 24-hour urinary protein levels increased significantly from the 4th week in anti-GBM model group than in control group [(52.27±10.50)mg/24h vs. (4.87±0.64)mg/24h, P<0.001], and then rose gradually until the 7th week [(255.80±9.79)mg/24h vs. (5.78±0.39)mg/24h, P<0.001]. Both the serum creatinine level and urea nitrogen level increased obviously in anti-GBM model group than in control group [(145.3±22.60)μmol/L vs. (36.81±2.21)μmol/L; (26.59±5.01)mmol/L vs. (6.92±0.27)mmol/L] with statistically significant difference (P<0.001). Compared with the control group, rats in anti-GBM model group produced high levels of circulating anti-pCol (24-38) IgG antibodies [(1.59±0.18) vs. (0.09±0.01)] with statistically significant difference (P<0.05). PAS staining showed glomerular sclerosis and diffuse crescent formation in anti-GBM model group; immunohistochemistry showed macrophage infiltration in glomerular; fluorescence staining showed obvious linear deposition of IgG in glomerular basement membrane. However, in the control group, PAS staining showed no abnormal glomerular, immunohistochemistry showed no macrophage infiltration, and fluorescence staining showed no IgG deposits on the glomerular basement membrane. Conclusions The animal model of anti-GBM disease may be successfully constructed by using polypeptide pCol (24-38) as antigen to immunize WKY rats. The preparation method of the antigen is simple, and so is valuable for designing new therapeutic strategies against anti-GBM disease.

Clinical and pathological features and mutational types of WT1 mutation-associated nephropathy / 中华儿科杂志

Objective@#To explore the clinical and pathological features and mutational types and their relations with WT1 mutation-associated nephropathy (WT1MAN).@*Methods@#The clinical and pathological data and the results of WT1 mutation analysis of the cases from Nanfang Hospital of Southern Medical University, Sun Yat-sen Memorial Hospital and The First Affiliated Hospital of Sun Yat-sen University whom we recruited recently and reported during the last ten years were analyzed.@*Results@#Totally, 20 cases (6 males and 14 females), included 5 newly diagnosed cases, were recruited. (1) Ten children were diagnosed with Denys-Drash syndrome (DDS): The median onset age of proteinuria was 1 year and 7 months. Diffuse mesangial sclerosis (DMS) were revealed in 3 cases, minimal lesions (MCD) in 4 cases, and focal segmental glomerulosclerosis (FSGS) in 1 case; renal pathology was not available in the other 2 cases. Glomerular basement membrane (GBM) thickening was observed in 2 cases. Calcineurin inhibitors (CNIs) were administered in 5 cases, complete remission of proteinuria was observed in 3 cases, partial remission in the other 2 cases. Genetic analysis revealed that six cases had WT1 missense mutation, 3 had nonsense mutation, and 1 had frameshift mutation. (2) Two cases were diagnosed with Frasier syndrome (FS): proteinuria was observed at 1 year and 1 month of age and 1 year and 9 months of age, respectively. FSGS with GBM layering were observed in both cases. They progressed to ESRD at 1 year and 6 months of age and 6 years and 6 months of age, respectively. CNI was tried in 1 case with partial proteinuria remission. Both patients were detected to have WT1 splice mutation. (3) Isolated nephropathy (IN) was observed in 8 cases: three had splice mutation, 5 had missense mutation. Of the 3 patients with splice mutation, one was found to have nephropathy and renal failure at the age of 5 months. The other two cases (1 was FSGS and another MCD), both had GBM layering. CNIs were tried on both of them, one got partial remission with normal renal function at the age of fourteen years, the other one had no response and entered ESRD at the age of 6 years and 9 months. Of the 5 cases with missense mutation, 3 had DMS, 2 of them entered ESRD within 6 months of age, another case had DMS entered ESRD at 9 years of age. One case with FSGS, was treated with CNIs and got complete remission.@*Conclusions@#Slow progression (7/10) nephropathy was observed in DDS patients. Missense mutation (11/20) was the most common type of WT1 variants, followed by splice mutation (5/20) in this group of patients. Early onset nephropathy (4/5), rapid progression (4/5) and GBM layering (4/4) wereobserved in patients with splice mutation. CNI was effective in reducing or even eliminating proteinuria in WT1 MAN patients (8/9).

The expression and significance of HMGB1,TLR4 and STAT3 in mousemodel of anti glomerular basement membrane glomerulonephritis / 国际检验医学杂志

Objective To study the expression and significance of HMGB1,TLR4 and STAT3 in the mouse model of anti glomerular basement membrane glomerulonephritis.Methods Totally 30 mice were randomly divided into normal group(control group),anti GBM glomerulonephritis model group(experimental group),PAS staining was used to observe the changes of glomerular basement membrane,HMGB1,p-STAT3 mRNA in renal tissue were detected by RT-PCR,HMGB1,TLR4,STAT3,p-STAT3 in renal tissue was detected by Western blot method.Results Compared with the control group,the experimental group of mice glomerular basement membrane thickening;the relative expression of HMGB1,TLR4,STAT3,p-STAT3 and HMGB1 mRNA,p-STAT3 mRNA in the kidney tissue of experimental group were significantly higher than the control group,the difference was statistically significant(P<0.05).The expression level of HMGB1 and TLR4,TLR4 and p-STAT3,HMGB1 and p-STAT3,HMGB1 mRNA and p-STAT3 mRNA in renal tissues of mice in experimental group,there were a positive correlation(r=0.401,P=0.005;r=0.399,P=0.005;r=0.412,P=0.004;r=0.398,P=0.005).Conclusion The inflammatory effect of HMGB1 in mice with anti glomerular basement membrane glomerulonephritis can activate STAT3 by binding to its receptor TLR4,so as to achieve anti glomerular basement membrane glomerulonephritis.

Nursing care of two cases of anti-glomerular basement membrane disease / 现代临床护理

Objective To summarize the experience in nursing 2 patients with anti-glomerular basement membrane disease.Method The nursing measures such as close observation of disease condition,careful nursing of medication,nursing during the treatment of double filtrated plasmapheresis and mental care to the patients and their family members.Results After treatment,the concentration of anti-GBM antibody was declined and the level of serum creatinine was also decreased.The renal function got rccovered to a certain extent.Conclusion Such nursing points as close observation of renal and pulmonary pathgenesis,timely and accurate administration of medicine according to doctor's orders and active observation and prevention of complication from double filtrated plasmapheresis are key.

Methodology establishment and application of therapeutic treatment on rats with anti-glomerular basement membrane nephritis / 中草药

Objective To establish a suitable model for therapeutic treatment on rats of anti-glomerular basement membrane nephritis. Methods Rabbit with rat glomerular basement membrane and freund’s adjuvant were immuned by multi-point subcutaneous injection biweekly, five times totally, and the antiserum was prepared. Experimental model for therapeutic treatment was established. Serum level of immune complex (CIC), intensity of immunofluorescence of glomerular basement membrane, lesion of kidney and glomerular basement membrane was measured by multiple intravenous injection of antiserum to rats to determine suitable experiment conditions including titer of antiserum, dose of antiserum, method and time of antiserum injection. The model was observed the efficacy using Gushen 2 as therapeutic drug. Results Rats with 4 mL antiserum (titer 1:4) by intravenous injection were immuned 4 times 3 d. Rat anti-glomerular basement membrane nephritis form on day 6, 8, and 10 since immunization; Pathogenic condition were relatively mild on day 6 since immunization and basically stable on day 8 and 10 since immunization. Verification tests showed that, Gushen 2 significantly reduced the 24 h urine protein excretion, relieved kidney lesion for 30 consecutive days, which had obvious therapeutic effect on rats with anti-glomerular basement membrane of nephritis. Conclusion Rats immuned with 4 mL antiserum (titer 1:4) by intravenous, immune points up to 4 times 3 d, rat anti-glomerular basement membrane nephritis model form which are suitable for therapeutic treatment of drug on day 8 since immunization.

Abnormal distribution of laminin α2 chain in glomerular basement membrane in membranous nephropathy / 临床与实验病理学杂志

To study the abnormal distribution of type Ⅳ collagen and laminin chains in glomerular basement membrane (GBM) in membranous nephropathy (MN).Methods 52 cases of MN were collected and staged according to electron microscopic morphological characteristics,and 10 cases of kidney tissues of minimal change disease were used as normal GBM control.Distribution pattern of or5 (Ⅳ) chain,laminin α5and β2 chains,and laminin α2 and β1 chains were detected using immunofluorescence method.Results In minimal change disease,α5 (Ⅳ) chain,laminin α5 and β2 chains all showed continuously linear positive expression along GBM,and laminin α2 and β1 chains were negatively expressed in GBM.In stage Ⅰ MN,α5 (Ⅳ) chain,laminin α.5 and β2 chains all showed continuous linear positive expression along GBM.In stage ⅡMN,the expression of α5 (Ⅳ) chain was increased and showed abundant spikes on the basis of continuous linear positive staining along GBM,and the expression of laminin α5 and β2chains was increased,and segmental spikes were seen on the basis of continuous linear positive staining along GBM.In stage ⅢMN,the expression of α5 (Ⅳ),laminin α5 and β2 chains was also enhanced and segmental double tracks were seen.The expression of laminin α2 chain was negative in GBM in stage ⅠMN,but granular positive expression along GBM was seen in stage Ⅱ and stage Ⅲ MN.No positive expression of laminin β1chain was seen in GBM in different stages in MN.Conclusion The GBM thickness in MN originates not only from intrinsic type Ⅳ collagen chains and laminin chains,but also from laminin α2chain,which only exist in glomerulus mesangium in normal condition.

Unusual Case of Posterior Reversible Encephalopathy Syndrome in a Patient with Anti-glomerular Basement Membrane Antibody Glomerulonephritis: A Case Report and Review of the Literature

Posterior reversible encephalopathy syndrome (PRES) is characterized by a clinical and radiological entity with the sudden onset of seizures, headache, altered consciousness, and visual disturbances in patients with the findings of reversible vasogenic subcortical edema without infarction. Hypertension, renal disease, and autoimmune disease are co-morbid conditions of PRES. Nevertheless, there have only been a few case reports of PRES in a patient with anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN). This paper presents the possible first Korean case of a 36-year-old woman with the striking features of PRES. She presented with a sudden onset of visual blindness, headache, and seizure. The brain MRI images revealed hyperintense lesions in both the occipital and parietal lobes, which suggested vasogenic edema. Three months before this presentation, she was diagnosed with anti-GBM GN. Since then, she underwent immunosuppression with cyclophosphamide and steroid, and hemodialysis for renal failure with a treatment of anti-GBM GN.

Productos finales de glicación (AGES) y la nefropatía diabética / Glycation end products (AGEs) and diabetic nephropathy

Los productos finales de glicación (AGEs) son un grupo heterogéneo de moléculas generadas por medio de reacciones no enzimáticas de glicación y de oxidación de proteínas, lípidos y ácidos nucleicos. La formación aumentada de AGEs ocurre en condiciones tales como la diabetes mellitus y el envejecimiento. AGEs median sus efectos a través de tres mecanismos principales: 1) entrecruzamiento con proteínas de la matriz extracelular, afectando las propiedades mecánicas de los tejidos, 2) entrecruzamiento con proteínas intracelulares alterando sus funciones fisiológicas y 3) unión a sus receptores de superficie RAGE para inducir múltiples cascadas de señales intracelulares. La acumulación de AGEs en las proteínas tisulares ha sido implicada en las complicaciones vasculares diabéticas, tales como la retinopatía, la nefropatía y la neuropatía. En la nefropatía diabética los AGEs contribuyen al desarrollo y progresión de esta enfermedad renal.

Advanced glycation end products (AGEs) are a heterogenous group of molecules that are generated through nonenzimatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation and accumulation of AGEs has been reported to occur in conditions such as diabetes mellitus as well as in natural aging. AGEs mediate their effects through three main mechanism: 1) cross linking extracellular (matrix) proteins thereby affecting tissue mechanical properties, 2) cross linking intracellular proteins thus altering their physiological functios and 3) binding to their cell surface receptor RAGE to inducing multiple intracellular signalling cascades. The accumulation of AGEs in tissue proteins has been implicated in diabetic vascular complications, such as retinopathy, nephropathy and neuropathy. In the diabetic nephropathy AGEs contribute to the development and progression of this renal disease.

Effects of mycophenolate mofetil on anti-glomerular basement membrane nephritis SD rats / 重庆医学

Objective To investigate the influence of mycophenolate mofetil(MMF) on blood and urine biochemical indica‐tors as well as the expressions of IL‐1 in anti‐glomerular basement membrane(GBM ) nephritis SD rats .Methods The SD rats were randomly divided into control group ,model group and MMF group .And then the models of SD rat anti‐GBM nephritis were estab‐lished by injecting rabbit anti‐SD rat GBM serum antibodies .The urinary protein and blood parameters were detected initially ,1st , 2nd ,3rd and 4th weeks after administration respectively .The expressions of IL‐1 and TGF‐β1 were detected by Elisa Kit and the re‐nal pathological changes were observed by HE and PAS staining .Results After treatment for 4 weeks by MMF ,the 24 h UP ,BUN and SCr levels were lower in MMF group than those of the model group(P<0 .05) .And the expressions of IL‐1 and TGF‐β1 were decreased in MMF group .The results of HE and PAS staining showed that in model group rats ,glomerular tuft morphology was destroyed and inflammatory cell infiltration was observed in the glomeruli .Some glomeruli had cellular crescent formation .Infiltra‐tion of inflammatory cells was also observed in the interstitium .MMF clearly improved these pathological changes overall ,with im‐provements noted in both glomerular and tubular degeneration as well as in the infiltration of inflammatory cells .Conclusion MMF shows certain renal protective effect on anti‐GBM nephritis SD rats .

One neonate with bullae of lung whose mother diagnosed with Goodpasture's syndrome during pregnancy:case report and review of the literatures / 中华围产医学杂志

Objective To summarize the clinical features and possible impacts of Goodpasture's syndrome in pregnancy on the pulmonary and kidney of the newborn and the mothers. Methods One patient diagnosed Goodpasture's syndrome in pregnancy hospitalized in Peking Union Medical College Hospital on August 23 in 2011 delivered a neonate with bullae of lung. And literatures including 8 cases of pregnancy complicated by Goodpasture's syndrome worldwide through Medline were reviewed. Results (1) Case report:one 31-year-old women presented with acute renal failure at 30+6 weeks of gestation and delivered a male infant with birth weight 1 900 g by caesarean section at 31+1 weeks of gestation. Diagnosis was confirmed as Goodpasture's syndrome with anti-glomerular basement membrane(GBM) antibodies in serum and renal biopsy after delivery. Then she was treated with methylprednisolone, cyclophosphamide, plasmapheresis and dialysis. The neonate showed the lung bullae in the right middle lobe and bilateral intraventricular hemorrhage but renal function was transient normal with anti-GBM as 113.1 EU/ml. The baby was treated by glucocorticoid for two months and clinical symptoms were improved. Anti-GBM antibodies and chest CT showed normal. After been followed up for two years, the baby was normal. (2) Literatures review:the main manifestations of Goodpasture's syndrome in pregnancy were malignant hypertension and renal failure but respiratory symptoms were not obvious. Treated with plasmapheresis, hematodialysis and glucocorticoid maybe have good effects. Most cases had premature delivery. Neonatal anti-GBM antibodies coming from mothers could result to cerebral, renal and pulmonary injury which could be treated by glucocorticoid. Conclusions The Clinical features of pregnancy complicating the Goodpasture's syndrome are malignant hypertension and renal failure. Diagnosis was depended on positive anti-GBM antibodies and renal pathological changes and treatment were depended on plasmapheresis, hematodialysis and glucocorticoid. Neonatal cerebral, renal and pulmonary injury resulting from anti-GBM antibodies coming from mothers should be followed up, and glucocorticoid should be taken if necessary.

Laboratory tests in autoimmune renal diseases:an update / 中华检验医学杂志

Autoimmune diseases are characterized by the presence of various autoantibodies and may cause injuries to multiple organs,with kidney as the most common and important organ involved.Autoantibodies are of great importance in the diagnosis,treatment and prognosis of autoimmune renal diseases.Lupus nephritis,anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and antiglomerular basement membrane (GBM) disease are the most common autoimmune renal diseases.Anti-C1q antibody,ANCA and anti-GBM antibody play important roles in those diseases,respectively.Appropriate and steady detecting methods are crucial to clinicians,and the results should also be interpreted with great cautions.

Clinical manifestations of IgA nephropathy combined with thin glomerular basement membrane nephropathy in children

BACKGROUND: Immunoglobulin A nephropathy (IgAN) and thin glomerular basement membrane nephropathy (TBMN) are the most common causes of persistent hematuria during childhood. The objective of this study is to determine the difference in clinicl features and laboratory findings between pediatric patients with IgA deposited TBMN and IgAN alone. METHODS: Between January 2000 and March 2009, 95 children were diagnosed with IgAN by renal biopsy. Clinical features and laboratory findings of patients with isolated IgAN and with IgAN plus TBMN were compared; the children diagnosed with IgAN were compared to 127 children who had been diagnosed with TBMN alone during the same period. RESULTS: There were 71 (74.7%) of a total 95 patients that were diagnosed with isolated IgAN (Group 1); in 24 (25.3%) of the 95 patients IgAN was combined with TBMN (Group 2). There was marked difference in the gender distribution between Group 2 and isolated TBMN patients. The degree of proteinuria and pathologic severity was higher in Group 1 compared with Group 2. Gross hematuria was present in both groups. There were no distinguishing features in the other laboratory parameters. CONCLUSION: Patients with both IgAN and TBMN seem to have similar clinical features to patients with isolated IgAN; however, the latter tend to have better pathologic and laboratory findings, compared to the patients with IgAN alone.

Analysis of ultrastructural glomerular basement membrane lesions and podocytes associated with proteinuria and sclerosis in Osborne-Mendel rats with progressive glomerulonephropathy

The renal glomeruli of 12 male Osborne-Mendel (OM) rats 3 to 24 weeks old were examined by electron microscopy. Effacement of podocyte foot processes (FPs) developed at 3 weeks of age and became progressively worse over time. Loss or dislocation of the slit membrane was also found. Vacuoles and osmiophilic lysosomes appeared in the podocytes starting at 6 weeks of age. Podocyte detachment from the glomerular basement membrane (GBM) was apparent at 18 weeks of age. Laminated GBM was occasionally observed in all animals. These features might lead to the development of spontaneous proteinuria and glomerulosclerosis in OM rats.