Nefropatía por IgA con microangiopatía trombótica / IgA nephropathy with thrombotic microangiopathy

INTRODUCTION: IgA nephropathy is the most common glomerulopathy in the world, it has a wide clinical expression, from asymptomatic to rapidly progressive glomerulonephritis. The definitive diagnosis is renal biopsy, within which the IgA pattern can be identified, including thrombotic microangiopathy. CLINICAL CASE: 28-year-old female patient, with a history of preeclampsia in the last pregnancy, presents high blood pressure, hematuria and proteinuria. Study begins with initially negative results. Renal biopsy confirms IgA nephropathy with thrombotic microangiopathy. DISCUSSION: Vascular damage is underestimated in IgA nephropathy. Thrombotic microangiopathy can be associated with various clinical manifestations, however when it is associated with IgA Nephropathy it is usually associated with proteinuria, arterial hypertension and elevation of creatinine. In the presence of microangiopathy, secondary causes must be ruled out. In general, there is no pathognomonic serological marker. Eventually patients could benefit from the use of eculizumab. CONCLUSION: IgA nephropathy is the most common glomerulopathy worldwide; there is a wide range of clinical presentations, among which thrombotic microangiopathy can be found. This presentation is associated with a higher risk of progression to end-stage renal disease.

INTRODUCCIÓN: La nefropatía por IgA es la glomerulopatía más frecuente en el mundo, tiene una amplia expresión clínica, desde asintomática hasta glomerulonefritis rápidamente progresivas. El diagnóstico definitivo es la biopsia renal, dentro de las cuales se puede identificar el patrón de la IgA, dentro de los cuales está la microangiopatía trombótica. CASO CLÍNICO: Paciente femenina 28 años, con antecedentes de preeclampsia en último embarazo, presenta hipertensión arterial, hematuria y proteinuria. Se inicia estudio con resultados inicialmente negativos. Biopsia renal confirma nefropatía por IgA con microangiopatía trombótica. DISCUSIÓN: En la nefropatía por IgA se subestima el daño vascular. La microangiopatía trombótica se puede asociar con varias manifestaciones clínicas, sin embargo, cuando está asociada a NIgA suele estar asociado con proteinuria, hipertensión arterial y elevación y creatinina. Ante la presencia de microangiopatía, se deben descartar causas secundarias de la misma. En general no existe un marcador serológico patognomónico. Eventualmente los pacientes se podrían beneficiar del uso de eculizumab. CONCLUSIÓN: La nefropatía por IgA es la glomerulopatía más frecuente a nivel mundial, existe una gran gama de presentaciones clínicas, dentro de las cuales se puede encontrar microangiopatía trombótica. Esta última presentación se asocia con mayor riesgo de progresión a enfermedad renal en etapa terminal.

Recognition of intestinal mucosal immunopathogenesis of IgA nephropathy: gut-derived IgA + plasma cells / 中华实用儿科临床杂志

Gut-derived IgA + plasma cells are the key to intestinal mucosal immunity.The intestinal flora and diet regulate the production of gut-derived IgA + plasma cells, which not only play an immune role in the intestinal mucosa, but also migrate to tissues or organs outside the intestine to regulate immune and inflammatory reactions by relying on the production of IgA antibodies or the secretion of cytokines and other non-antibody effects, and act as a protective or pathogenic factor in various diseases.The pathogenic effect of intestinal mucosal immune imbalance in IgA nephropathy (IgAN) has been a concern.IgA + plasma cells increase in intestinal lamina propria of high serum IgA mice with the increase of abnormally glycosylated IgA1.The long-lived plasma cells increase, and interleukin-6 is inhibited in IgAN patients.However, it remains unclear whether gut-derived IgA + plasma cells migrate to kidneys to promote disease progression.This article reviews the relevant research progress on the immunopathologic effects and mechanisms of gut-derived IgA + plasma cells in the intestinal mucosa of IgAN.

Relationship between expressions of P21,P27 and PCNA in glomerular mesangial tissue and poor renal prognosis in patients with IgA nephropathy / 中国免疫学杂志

Objective:To explore the relationship between the expressions of P21,P27 and proliferating cell nuclear antigen(PCNA)in glomerular mesangial tissue and poor renal prognosis in patients with immunoglobulin A(IgA)nephropathy.Methods:A total of 145 patients with IgA nephropathy treated in Xiaogan Central Hospital from April 2017 to August 2019 were selected as the research object.The expressions of P21,P27 and PCNA in glomerular mesangial tissue were detected by immunohistochemistry.All patients were followed up for 24 months,and the prognosis were counted.The expressions of P21,P27 and PCNA in glomerular mesangial tissue of patients with different prognosis were compared and the influencing factors of poor prognosis in patients with IgA nephropathy were analyzed by Logistic regression analysis.Results:The expression rates of P21,P27 and PCNA positive cells in glomerular mesangial tissue of patients with IgA nephropathy were(38.69±6.83)%,(55.94±8.08)%,(33.47±5.72)%,respectively.The incidence rete of poor prognosis in patients with IgA nephropathy was 17.24%,and the expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of patients with poor prognosis were higher than those in good prognosis group(P<0.05),while the expression rate of P27 positive cells was lower than that in good prognosis group(P<0.05).Logistic multiple regression analysis showed that elevated diastolic blood pressure,increased 24 h proteinuria,mesangial cell proliferation,segmental glomerulosclerosis,renal tubular atrophy/interstitial fibrosis,crescentic body,increased expression rates of P21 and PCNA positive cells and decreased expression rate of P27 positive cells were all risk factors affecting the poor prognosis of patients with IgA nephropathy(P<0.05).Conclusion:There are positive expressions of P21,P27 and PCNA in glomerular mesangial tissue of IgA nephropathy.The expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of of patients with poor prognosis of IgA nephropathy are higher than those with good prognosis,while the expression rate of P27 protein positive cells is lower than those with good prognosis,which are risk factors for poor prognosis of patients with IgA nephropathy.

Analysis of LU Keda's Experience in Treating IgA Nephropathy with Yiqi Yangyin Qufeng Prescription / 浙江中医药大学学报

[Objective]To explore Professor LU Keda's clinical experience in treating IgA nephropathy with Yiqi Yangyin Qufeng prescription.[Methods]Through outpatient learning with teacher,consulting IgA nephropathy related literature,Professor LU's clinical experience in treating IgA nephropathy with Yiqi Yangyin Qufeng Prescription was summarized,and one medical case was provided to support the treatment.[Results]Professor LU points out that the early IgA nephropathy patients are deficient in spleen and kidney,and always invaded by wind easily.He applies the thought of syndrome differentiation and prescription called"state target binding"from Academician TONG Xiaolin,taking"Qi and Yin deficiency syndrome"as the state,and the physical and chemical indexes"proteinuria and hematuria"as the target,using Yiqi Yangyin Qufeng Prescription for treatment.The medical case mentioned later was identified as early-stage IgA nephropathy,belonged to Qi and Yin deficiency syndrome.The treatment was to invigorate the spleen and tonify Qi,nourish Yin and promote body fluid and dispel wind.It had great curative effect by using Yiqi Yangyin Qufeng Prescription.[Conclusion]Professor LU's experience in establishing the treatment of IgA nephropathy from the perspective of"state target syndrome differentiation"is worth learning and inheriting.

Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy / 中国药房

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

TCM Treatment of Podocyte Injury in IgA Nephropathy Based on Multiple TCM Theories： A Review / 中国实验方剂学杂志

IgA nephropathy is the most common primary glomerular disease in China. Its clinical manifestations are mainly proteinuria， hematuria， hypertension， edema， hyperuricemia， etc. Most patients have hidden onset. 30%-40% of patients develop into end stage renal disease 10-20 years after diagnosis and rely on dialysis or kidney transplantation to maintain their lives， which is extremely harmful. Proteinuria is a common clinical manifestation of this disease， and most patients have small-to-moderate amounts of proteinuria， while 10%-24% of patients have large amounts of proteinuria. Proteinuria is the main risk factor affecting the progression of renal function in IgA nephropathy. Podocytes are the terminal part of the glomerular filtration barrier， and various factors can affect the fusion and detachment of podocyte processes that occur after podocyte injury. They are common histological lesions in IgA nephropathy and are key factors leading to proteinuria and the continuous progression of the disease. At present， Western medicine lacks targeted treatment for podocyte injury， with limited intervention methods. Drugs such as glucocorticoids are often used for treatment， and there are many adverse reactions. Based on the physiological function of podocytes， pathological and physiological changes after injury， and histological morphology of this disease， it is believed that it is closely related to traditional Chinese medicine's "Xuanfu Theory" "Kidney Collateral Syndrome" "Collateral Disease Theory"， and "Dry Blood Theory". More and more studies have shown that traditional Chinese medicine， which has the characteristics of multiple links， pathways， and targets， has a significant therapeutic effect on podocyte injury in IgA nephropathy. It can protect podocytes and reduce proteinuria and has good application and research prospects. This article systematically summarizes the mechanism and morphological changes of podocyte injury in IgA nephropathy， the understanding of podocyte injury in traditional Chinese medicine theory， and the research progress in traditional Chinese medicine treatment of podocyte injury in IgA nephropathy， so as to provide a reference for further research and application of traditional Chinese medicine intervention in podocyte injury in IgA nephropathy.

Role of NLRP3 Inflammasome in IgA Nephropathy and Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

IgA nephropathy is recognized as the most common primary glomerular disease， with up to 20%-40% of patients developing end-stage kidney disease within 20 years of onset. The deposition of IgA1-containing immune complexes targeting glycosylation defects in the mesangial region and the subsequent inflammation caused by T lymphocyte activation are considered as the main causes of IgA nephropathy， and innate immunity is also involved in the pathogenesis. Nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） is a newly discovered pattern recognition receptor expressed in renal intrinsic cells such as renal tubular epithelial cells， mesangial cells， and podocytes. Activated by external stimuli， NLRP3 can form NLRP3 inflammasomes with apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC）. The NLRP3 inflammasome can activate cysteine aspartate-specific protease-1 （Caspase-1）， causing the maturation and release of interleukin-18 （IL-18） and interleukin-1β （IL-1β） involved in inflammation. Increasing evidence has suggested that NLRP3 inflammasomes are involved in the pathogenesis and progression of IgA nephropathy and associated with the damage of renal intrinsic cells such as podocytes， mesangial cells， endothelial cells， and renal tubular epithelial cells. Chinese medicine can regulate inflammatory cytokines and their signaling pathways by acting on NLRP3 inflammasomes and related molecules， exerting therapeutic effects on IgA nephropathy. This article introduces the role of NLRP3 inflammasomes in IgA nephropathy and reviews the clinical and experimental research progress of Chinese medicine intervention in IgA nephropathy via NLRP3 inflammasomes， aiming to provide a reference for further research and application of Chinese medicine intervention in the NLRP3 inflammasome as a new therapeutic target.

Crescentic IgA nephropathy following SARS-CoV-2 vaccination. Report of a case / Nefropatía por IgA extracapilar luego de la vacunación contra el SARS-CoV-2. Reporte de un caso

ABSTRACT Introduction: Studies have shown that the frequency of acute kidney injury (AKI) increases in patients with COVID-19. Acute tubular necrosis has been reported to be the most common damage in these patients, probably due to impaired renal perfusion. On the other hand, different complex pathophysiological processes may be involved due to viral infection's direct effects on the renin-angiotensin-aldosterone system, the activation of coagulopathy, the cytokine storm, and the activation of the immune system. Many glomerular diseases may be seen in these patients, like anca-associated vasculitis, membranous glomerulonephritis, and IgA nephropathy. Clinical case: We present a newly diagnosed crescentic IgA nephropathy (IgAN) case after a SARS-CoV-2 infection and vaccination. A 31-year-old man with no medical history presented with gross hematuria 24 hours after SARS-CoV-2 infection. Hematuria regressed spontaneously within three days. He was vaccinated with two doses of CoronaVac (Sinovac) three months after he had been infected by SARS-CoV-2. Then he was vaccinated with the Pfizer-BioNTech COVID-19 vaccine one month after the second dose of CoronaVac (Sinovac) vaccine. He presented with gross hematuria and subnephrotic proteinuria 24 hours after the first dose of the Pfizer-BioNTech COVID-19 vaccine. A kidney biopsy was performed and showed crescentic IgA nephropathy (IgAN). He was started on methylprednisolone and angiotensin receptor blocker. Patients who receive mRNA-based vaccines demonstrate robust antibody production against the receptor-binding domain (RBD) of the S1 protein. Similar to natural infection, due to the intense stimulation of immune response from mRNA-based vaccines compared to other vaccines, the patients may produce de novo antibodies, leading to IgA-containing immune-complex deposits. Conclusions: This case highlights the immunological effects of the novel mRNA-based SARS-CoV-2 vaccines. Nephrologists should be aware of new-onset hematuria or proteinuria after SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccine.

RESUMEN Introducción: Los estudios han demostrado que la frecuencia de insuficiencia renal aguda (IRA) aumenta en pacientes con COVID-19. Se ha informado que la necrosis tubular aguda es el daño más común en estos pacientes, probablemente debido a la alteración de la perfusión renal. Por otro lado, pueden estar involucrados diferentes procesos fisiopatológicos complejos, debido a los efectos directos de la infección viral sobre el sistema renina-angiotensina-aldosterona, la activación de la coagulopatía, la tormenta de citoquinas y la activación del sistema inmunológico. En estos pacientes se pueden observar muchas enfermedades glomerulares, como vasculitis asociada a anca, glomerulonefritis membranosa y nefropatía por IgA. Caso clínico: Presentamos un caso de nefropatía IgA extracapilar (NIgA) de nuevo diagnóstico tras una infección por SARS-CoV-2 y vacunación. Un hombre de 31 años sin antecedentes médicos presentó hematuria macroscópica 24 horas después de la infección por SARS-CoV-2. La hematuria remitió espontáneamente en 3 días. Fue vacunado con dos dosis de CoronaVac (Sinovac) tres meses después de haber sido infectado por el SARS-CoV-2. Luego fue vacunado con la vacuna Pfizer-BioNTech COVID-19, un mes después de la segunda dosis de la vacuna CoronaVac (Sinovac). Presentó hematuria macroscópica y proteinuria no nefrótica 24 horas después de la primera dosis de la vacuna Pfizer-BioNTech COVID-19. Se realizó una biopsia renal que mostró NIgA extracapilar. Comenzó con metilprednisolona y bloqueador del receptor de angiotensina. Los pacientes que reciben vacunas basadas en ARNm demuestran anticuerpos contra el dominio de unión al receptor (RBD) de la proteína S1. De manera similar a la infección natural, debido a la fuerte estimulación de la respuesta inmunitaria de las vacunas basadas en ARNm en comparación con otras vacunas, los pacientes pueden producir anticuerpos de novo, lo que lleva a depósitos de complejos inmunitarios que contienen IgA. Conclusiones: Este caso destaca los efectos inmunológicos de las nuevas vacunas contra el SARS-CoV-2 basadas en ARNm. Los nefrólogos deben estar al tanto de la aparición de hematuria o proteinuria luego de la infección por SARS-CoV-2 o la vacuna contra el SARS CoV-2 basada en ARNm.

Nefropatía por IgA en una adolescente con lupus eritematoso sistémico juvenil. Reporte de caso

Introducción: El lupus eritematoso sistémico juvenil (LESJ) es una enfermedad autoinmunitaria, multisistémica, caracterizada por la producción de autoanticuerpos y el desarrollo frecuente de glomerulonefritis mediada por inmunocomplejos. La nefritis lúpica es una complicación frecuente y grave del LESJ, con alta morbilidad, siendo causa de insuficiencia renal terminal en muchos de estos pacientes. La nefropatía por IgA representa la etiología más común en la población general y raramente se asocia con LESJ. Caso clínico: adolescente femenino con LESJ en quien se diagnosticó nefritis no lúpica (nefropatía por IgA). Conclusiones: El diagnóstico anatomopatológico es clave para establecer el pronóstico y planificar el tratamiento.

Introduction: Juvenile systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease characterized by the production of autoantibodies and the frequent development of immune complex-mediated glomerulonephritis. Lupus nephritis is a frequent and serious complication of JSLE, has a high associated morbidity rate, and is the cause of end-stage renal failure in many of these patients. IgA Nephropathy represents the most common etiology in the general population and is rarely associated with JSLE. Clinical case: a female adolescent with JSLE who was diagnosed with non-lupus nephritis (IgA nephropathy). Conclusions: The anatomopathological diagnosis is key to establish the prognosis and plan the treatment.

Clinicopathologic features and risk factors of primary IgA nephropathy with foot process effacement / 安徽医科大学学报

Objective To investigate the clinical and pathological features and risk factors of primary IgA nephrop-athy(IgAN)with foot process effacement(FPE).Methods The clinical and Oxford-type pathological data of 300 patients diagnosed with primary IgAN by renal biopsy were retrospectively analyzed,and the influential factors of IgAN foot process fusion were analyzed by multivariate logistic regression with significant clinical indicators.Results 300 cases of adult IgAN diagnosed by renal puncture biopsy were included,the extensive FPE group accounted for 15％.156 cases(52％)were female and 144 cases(48％)were male.The median age of onset was 36(30,50)years.The median duration of renal biopsy was 8(1,24)months.The proportion of nephrotic syndrome in the extensive fusion group was higher(55.6％vs 6.7％,P＜0.05).There was no significant difference in the propor-tion of IgAN with hypertension among different degrees of FPE(P=0.092),but the systolic and diastolic blood pressure in the extensive FPE group were higher than those in the mild FPE group(P＜0.05).The levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-c),and 24-hour urinary protein in the extensive FPE group were higher(P＜0.05),but the levels of albumin,estimated glomerular filtration rate(eGFR)and hyperuricemia were low(P＜0.05).There were no significant differences in hemoglobin,creatinine,and uric acid levels between the two groups(P＞0.05).There was a higher proportion of endothelial cell prolifera-tion(E1),segmental sclerosis or adhesion(S1),and cellular or cellular fibrous crescents(C1-2)in the extensive FPE group(P＜0.05),while there was no significant difference in tubular atrophy or interstitial fibrosis(T1-2)between the two groups(P＞0.05).Univariate logistic regression analysis showed that diastolic blood pressure,eGFR,TC,TG,and LDL-c were associated with extensive FPE in IgAN patients.Multivariate logistic regression a-nalysis showed that elevated TC(OR=2.135,95％CI 1.095-4.164,P=0.026)was an independent risk factor for extensive fusion of the foot process.Conclusion Compared with mild FPE,IgAN patients with extensive FPE had higher rates of blood pressure,blood lipid,nephrotic syndrome and hyperuricemia,slightly worse renal func-tion,and more severe pathological manifestations of the Oxford-type.Elevated TC is an independent risk factor for extensive FPE in IgAN patients.

Construction a Risk Prediction Model of IgA Nephropathy Proteinuria Treated by Traditional Chinese Medicine Based on Random Survival Forest Model / 世界科学技术-中医药现代化

Objective Constructing a risk prediction model of IgA nephropathy proteinuria treated by traditional Chinese medicine based on random survival forest model,Screening prognostic risk factors of IgA nephropathy proteinuria.Methods Collecting retrospectively clinical data of 129 cases diagnosed with IgA nephropathy,randomly divided them into training set(60%)and test set(40%).The risk prediction model of IgA nephropathy proteinuria was constructed in the training set with the random survival forest model,and the prognostic risk factors were screened by VIMP method.The accuracy of risk prediction model was validated in the test set with time-dependent ROC curve(tdROC).Results According to the result of VIMP,the prognostic risk factors for IgA nephropathy proteinuria are in the order of eGFR,hypertension,traditional Chinese medicine,24 hUPRO>1 g,genomo sclerosis ratio,Lee grading,fat,hyperlipidemia,hypertrophymia,hyparmane ledmia,Anemia,age and gender.The eGFR was negatively and non-linearly associated with the risk rate of developing persistent proteinuria.Glomerulosclerosis ratio greater than 0.3 is approximately linearly and positively associated with the risk rate of persistent proteinuria.Conclusion Random survival forest model has good predictive performance in the risk prediction model of IgA nephropathy proteinuria treated by traditional Chinese medicine.This risk model can determine the result of IgA nephropathy treated by traditional Chinese medicine,and which is helpful for clinical follow-up monitoring and formulation of individualized treatment plans.

Construction of Item Weights of Qi Yin Deficiency Syndrome in IgA Nephropathy Based on Delphi Method and Analytic Hierarchy Process / 世界科学技术-中医药现代化

Objective To establish the diagnostic criteria of deficiency of Qi and Yin in IgA nephropathy by combining Delphi method with analytic hierarchy process.Methods After literature research,an item pool of Qi and yin deficiency syndrome was formed.Based on this item pool and expert discussion,an expert questionnaire was formed.Two rounds of Delphi method were used to conduct expert questionnaire survey,and then the weight value of the items was calculated by AHP.Finally,a diagnostic questionnaire of Qi and yin deficiency syndrome in IgA nephropathy was formed,which laid a foundation for the final formation of diagnostic criteria.Results Through Delphi and analytic hierarchy process,the following 12 items and their weights were finally obtained:①mental fatigue:13.1205%;②Weak waist and knees:7.8514%;③Dry mouth or throat:10.6984%;④Hand foot heart heat:8.985%;⑤Tinnitus:4.0495%;⑥Susceptible to cold:8.8027%;⑦Spontaneous or night sweat:9.4594%;⑧Yellow or red urine:4.7458%;⑨Pale red tongue:6.906%;⑩Fat tongue:7.159%;?Less moss or thin white moss:8.947%;?Weak or thin pulse:9.275%.Conclusion Through the combination of Delphi method and analytic hierarchy process,the qualitative analysis and quantitative evaluation of each item of Qi and yin deficiency syndrome in IgA nephropathy were carried out,and the best item and specific weight of Qi and yin deficiency syndrome in IgA nephropathy were obtained,providing a reference for the formation of future standards.

To Explore the Mechanism of Tonifying Kidney and Promoting Pharynx Prescription in the Treatment of IgA Nephropathy Based on TLR4 Signaling Pathway / 世界科学技术-中医药现代化

Objective To investigate the effect of tonifying kidney and promoting pharynx prescription on IgA nephropathy model rats and the mechanism of regulating the TLR4 signaling pathway.Methods After SD rats were randomly divided into groups,the rat model of IgA nephropathy was replicated.After the medication,urinary RBC,UTP,blood creatinine,urea nitrogen,renal tissue TLR4,MyD88,NF-κB,MCP-1 expression,C1GALT1 and cosmoc mRNA expression in peripheral blood,TLR4,NF-κB and IL-6 in serum were observed.Results ①Compared with the blank group,urinary RBC,UTP,and renal tissue TLR4,MyD88 and NF-κB,MCP-1 expression,C1GALT1 and cosmoc mRNA expression in peripheral blood,TLR4,NF-κB and IL-6 in serum increased in the model group(P<0.05).②Compared with the model group,UTP,urinary RBC,renal tissue TLR4,MyD88 and NF-κB,MCP-1 expression,C1GALT1 and cosmoc mRNA expression in peripheral blood,the content of TLR4 and NF-κB,IL-6 were decreased(P<0.05)in tonifying kidney and promoting pharynx prescription group;There was no significant change in renal function.Conclusions ①The tonifying kidney and promoting pharynx prescription can effectively reduce hematuria and proteinuria in rats with IgA nephropathy.②The tonifying kidney and promoting pharynx prescription can reduce renal injury by improving the immune response mediated by TLR4 Signal transduction system induced by mucosal infection and reducing abnormal glycosylation IgA1 by adjusting key enzyme C1GalT1 and molecular companion Cosmc in IgA1 glycosylation process.

Bushen Jianpi Jiedu Liyan Formula Regulates Homing-associated Cell Adhesion Molecules in Rat Model of IgA Nephropathy / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Bushen Jianpi Jiedu Liyan formula on the expression of integrin alpha 4 beta 1 （α4 β1）， vascular cell adhesion molecule-1 （VCAM-1）， stromal-derived factor-1 （SDF-1）， and chemokine receptor-4 （CXCR4） in the small intestine and bone marrow of the rat model of immunoglobulin A（IgA） nephropathy. MethodA total of 120 male SD rats were used to establish the IgA nephropathy model by intragastric administration of bovine serum albumin （BSA）， subcutaneous injection of CCl4， and tail vein injection of lipopolysaccharide （LPS）. The successfully modeled rats were randomized into blank， model， lotensin （63 mg·kg-1）， and low-， medium-， and high-dose （10.4， 20.81， 41.62 g·kg-1， respectively） Bushen Jianpi Jiedu Liyan formula groups （n=16）. The rats were treated with corresponding drugs according to their body weight. After 7 weeks of administration， the rats were sacrificed for the collection of samples， and the protein and mRNA levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the small intestine and bone marrow were determined by immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed increased red blood cell count in the urine at the 10th， 12th， 14th， 16th weeks （P<0.01）， and such increases were reduced in the drug intervention groups （P<0.05）， especially in the medium-dose Bushen Jianpi Jiedu Liyan formula group （P<0.05）. Compared with those in the blank group， the protein levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria in the model group were up-regulated （P<0.05）， and such un-regulations were inhibited in the drug intervention groups （P<0.05）. Compared with the model group， medium-dose Bushen Jianpi Jiedu Liyan formula down-regulated the protein levels of SDF-1 and CXCR4 in the intestinal lamina propria （P<0.05）. Compared with the blank group， the model group showed down-regulated mRNA levels of α4 β1 and SDF-1 and up-regulated mRNA levels of VCAM-1 and CXCR4 （P<0.05）. Compared with the model group， the drug intervention groups showed down-regulated mRNA levels of SDF-1 and CXCR4 （P<0.05）. ConclusionBushen Jianpi Jiedu Liyan formula regulates the expression of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria to inhibit the homing effect of plasma cells， which may be associated with the Toll-like receptor-mediated activation of immune response. Bushen Jianpi Jiedu Liyan formula can down-regulate the expression of adhesion molecules to inhibit the proliferation of plasmocytes in circulation， so as to reduce the renal injury of IgA nephropathy.

Notoginsenoside R_1 interferes with renal oxidative stress and Nrf2/HO-1 signaling pathway to alleviate kidney injury in mice with IgA nephropathy and its mechanism / 中国中药杂志

The purpose of this study was to investigate the effect of notoginsenoside R_1(NGR_1) on alleviating kidney injury by regulating renal oxidative stress and the Nrf2/HO-1 signaling pathway in mice with IgA nephropathy(IgAN) and its mechanism. The mouse model of IgAN was established using a variety of techniques, including continuous bovine serum albumin(BSA) gavage, subcutaneous injections of carbon tetrachloride(CCl_4) castor oil, and tail vein injections of lipopolysaccharide(LPS). After successful modeling, mice with IgAN were randomly separated into a model group, low, medium, and high-dose NGR_1 groups, and a losartan group, and C57BL6 mice were utilized as normal controls. The model and normal groups were given phosphate buffered saline(PBS) by gavage, the NGR_1 groups were given varying dosages of NGR_1 by gavage, and the losartan group was given losartan by gavage for 4 weeks. The 24-hour urine of mice was collected after the last administration, and serum and kidney tissues of mice were taken at the end of the animal experiment. Then urine red blood cell count(URBCC), 24-hour urine protein(24 h protein), serum creatinine(Scr), and blood urea nitrogen(BUN) levels were measured. The enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of galactose-deficient IgA1(Gd-IgA1), kidney injury molecule 1(Kim-1), and neutropil gelatinase-associated lipocalin(NGAL) in the mouse serum. The assay kits were used to detect the levels of malondialdehyde(MDA) and superoxide dismutase(SOD), and immunofluorescence(IF) was used to detect the expression level of glutathione peroxidase 4(GPX4) in the mesangial region. Western blot was used to detect the protein expression of nuclear transcription factor E2 related factor 2(Nrf2)/heme oxygenase 1(HO-1) signaling pathway in the renal tissue. Hematoxylin-eosin(HE) staining was used to observe pathological alterations in the glomerulus of mice. The results revealed that, as compared with the model group, the serum Gd-IgA1 level, URBCC, 24 h protein level, renal damage markers(Kim-1 and NGAL) in the high-dose NGR_1 group decreased obviously and renal function indicators(BUN, Scr) improved significantly. The activity of SOD activity and expression level of GPX4 increased significantly in the high-dose NGR_1 group, whereas the expression level of MDA reduced and protein expression levels of Nrf2 and HO-1 increased. Simultaneously, HE staining of the renal tissue indicated that glomerular damage was greatly decreased in the high-dose NGR_1 group. In conclusion, this study has clarified that NGR_1 may alleviate the kidney injury of mice with IgAN by activating the Nrf2/HO-1 signaling pathway, improving antioxidant capacity, and reducing the level of renal oxidative stress.

Effect of Dahuang Xiezhuo Prescription on Renal Tubular Function in Patients with IgA Nephropathy Complicated with Hyperuricemia / 中国实验方剂学杂志

ObjectiveTo observe the effect of Dahuang Xiezhuo prescription on the clinical symptoms， blood uric acid， and renal tubular function of patients with immunoglobulin A （IgA） nephropathy in stages 1-2 of chronic kidney disease （CKD） complicated with hyperuricemia （HUA）. MethodSixty patients with IgA nephropathy in stages 1-2 of CKD complicated with HUA of spleen and kidney deficiency and combined turbidity and blood stasis syndromes were randomly divided into an observation group and a control group， with 30 cases in each group. The patients in the control group received basic treatment， i.e.， losartan potassium tablets 50-100 mg/time， once per day， and sodium bicarbonate tablets 0.5 g/time， three times per day by oral administration， combined with low-salt， low-fat， and low-purine diet. The patients in the observation group received Dahuang Xiezhuo prescription on the basis of basic treatment， one dose per day， twice a day in the morning and evening with warm water. Both groups were treated for two months. The total scores of traditional Chinese medicine（TCM）syndrome， blood pressure， 24 h urinary protein （24 h UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr） ［glomerular filtration rate （eGFR） was calculated by CKD-epidemiology collaboration （CKD-EPI） formula］， serum uric acid （SUA）， and renal tubular function indexes ［urinary α1-microglobulin （α1-MG）， urinary β2-microglobulin （β2-MG）， urinary kidney injury molecule-1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL）］ of the two groups before treatment and two months after treatment were recorded. The clinical efficacy of the two groups was evaluated two months after treatment. ResultAfter 2 months of treatment，the total effective rate in the observation group was 81.48%（22/27），higher than 50.00%（14/28） in the control group（χ2 =6.661，P<0.05）. The total scores of TCM syndrome， 24 h UTP， and SUA in the observation group and the observation group were lower than those before treatment （P<0.05）， and compared with the control group after treatment， the observation group decreased more significantly （P<0.05）. After treatment， the blood pressure in the observation group and the observation group was lower than that before treatment （P<0.05）， and there was no significant difference in blood pressure between the two groups after treatment. After treatment， the levels of urinary α1-MG， β2-MG， KIM-1， and NGAL in the two groups were lower than those before treatment （P<0.05）， and the observation group was lower than the control group after treatment （P<0.05）. There were no significant inter-group and intra-group differences in BUN， SCr， and eGFR levels before and after treatment. There were no obvious abnormalities in blood routine， liver function， and electrolytes before and after treatment in the two groups， and no adverse reactions such as allergies occurred. ConclusionDahuang Xiezhuo prescription can effectively improve the clinical symptoms of IgA nephropathy with HUA （CKD1-2） patients with spleen and kidney deficiency and combined turbidity and blood stasis syndromes， reduce blood uric acid level， alleviate renal tubular injury， and protect the kidney. The curative effect is better than that of basic treatment.

Effect of Modified Shengjiangsan on Gd-IgA1 in IgA Nephropathy Rats： Based on C1GALT1/C1GALT1C1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveThe effect of modified Shengjiangsan on immunoglobulin A （IgA） nephropathy was observed. The microRNA-148b （miRNA-148b）， interleukin 6 （IL-6）， core 1 beta 1，3-galactosyltransferase （C1GALT1）， molecular chaperone Cosmc （core1β3-Gal-T-specific molecular chaperone C1GALT1C1）， and galactose-deficient IgA1 （Gd-IGA1） in serum and kidney tissues of IgA nephropathy rats were detected to explore the underlying mechanism. The result is expected to lay a scientific basis for clinical application of modified Shengjiangsan in the treatment of IgA nephropathy. MethodA total of 42 SPF male SD rats were randomized into the normal group （8rats） and modeling group （34 rats） with the random number table method. After one week of adaptive feeding， rats for modeling were given bovine serum albumin （BSA， gavage）， lipopolysaccharide （LPS， injection into tail vein）， carbon tetrachloride （CCl4， subcutaneous injection）， and castor oil to induce IgA nephropathy. After modeling， two rats were randomly selected to test the modeling outcome. Then the model rats were classified into the model group， low-dose Chinese medicine group （modified Shengjiangsan，6.27 g·kg-1）， high-dose Chinese medicine group （modified Shengjiangsan，12.54 g·kg-1）， and benazepril group （10 mg·kg-1） with the random number table method， 8 in each group. The administration （gavage， once a day） lasted 4 weeks. The 24-h urinary total protein （24 h-UTP） was detected at the end of the 1st， 9th， and 13th week of the experiment. At the 14th week， after anesthesia， femoral artery blood was collected and centrifugated. The supernatant was collected to detect albumin （ALB）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. The expression levels of IL-6 and Gd-IGA1 were determined by enzyme-linked immunosorbent assay （ELISA）. Based on hematoxylin-eosin （HE）/Masson/periodic Schiff-methenamine silver （PASM） staining， the pathological changes of renal tissues were observed. Ultrastructural changes of glomeruli were observed by transmission electron microscopy. The expression of miRNA-148b， IL-6， C1GALT1， and C1GALT1C1 was detected by immunohistochemistry. The mesangial area of the glomeruli was observed by immunofluorescence. Real-time polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of mirNA-148b， IL-6， C1GALT1， and C1GALT1C1， and Western blot was used to detect the protein levels of IL-6， C1GALT1， and C1GALT1C1. ResultCompared with normal group， the model group showed increase in the content of 24 h-UTP， SCr， ALT， IL-6， and GD-IGA1 （P<0.05）， decrease in ALB content （P<0.05）. Moreover， rats in the model group demonstrated hyperplasia of glomerular mesangial cells， thickening of mesangial area， podocyte foot process effacement， and a large number of granular IgA immune complex in the mesangial area. In addition， the model group showed increase in the expression of IL-6 in mesangial area and podocytes， decrease in the expression of C1GALT1 and C1GALT1C1 in mesangial area and podocytes， enhanced expression of IL-6 mRNA and miRNA-148b （P<0.01）， weakened expression of C1GALT1 mRNA and C1GALT1C1 mRNA （P<0.01）， rise of IL-6 protein expression （P<0.01）， and reduction in the protein expression of C1GALT1 and C1GALT1C1 （P<0.01）. Compared with the model group， modified Shengjiangsan decreased the content of 24 h-UTP， SCr， ALT， IL-6， and Gd-IGA1 （P<0.05） and increased the content of ALB （P<0.05， P<0.01）. Moreover， with the treatment of this Chinese medicine， the pathological damage was significantly alleviated and the deposition of IgA immune complex in basement membrane was reduced. The expression of IL-6 in the mesangial area and podocytes of rats was decreased， and the expression of C1GALT1 and C1GALT1C1 in the mesangial area and podocytes of rats was increased. Moreover， the expression of IL-6 mRNA and miRNA-148b was decreased （P<0.01）， and the expression of C1GALT1 mRNA and C1GALT1C1 mRNA was increased （P<0.01）. The protein expression of IL-6 was decreased （P<0.05， P<0.01）， and the protein expression of C1GALT1 and C1GALT1C1 was enhanced （P<0.05， P<0.01）. The Chinese medicine group showed obvious dose-effect trend. ConclusionModified Shengjiangsan may reduce the expression of miRNA-148b and IL-6 in serum and kidney tissue of IgA nephropathy rats， restore the expression of C1GALT1 and C1GALT1C1， and decrease the generation of Gd-IGA1， so as to reduce renal pathological damage and proteinuria， protect the kidney protection， and finally delay the disease progression. Moreover， the effect is enhanced with the rise of dose.

Establish a diagnosis differential model for IgA nephropathy and non-IgA nephropathy by machine learning / 中华检验医学杂志

Objective:To establish a differential diagnosis model for IgA nephropathy and non-IgA nephropathy based on machine learning algorithms.Methods:Retrospective study adopted,from 2019 to 2020,260 patients were referred to the Department of Nephrology at the First Affiliated Hospital of Kunming Medical University, the First People′s Hospital in Yunnan province, and Yan′an Hospital of Kunming city. All patients were diagnosed by renal pathology, 130 cases of primary IgA nephropathy, the 130 cases of non-IgA nephropathy. Collection of materials, including gender and age, 28 clinical data, and routine laboratory test results,the sex ratio of IgA nephropathy group and non-IgA nephropathy group were 59∶71 and 64∶66 respectively, the ages were 37.20 (21.89, 53.78) and 43.30 (27.77, 59.18) years, respectively. 260 patients were divided into a training set (70%, 182 cases) and a test set (30%, 78 cases). Using the decision tree, random forests, support vector machine, extreme gradient boosting to establish a differential diagnosis model for IgA nephropathy and non-IgA nephropathy. Based on the true positive rate, true negative rate, false-positive rate, false-negative rate, accuracy, subjects features work area under the curve(AUC), the precision ratio, recall ratio, and F1 score, comprehensively evaluate the performance of each model, finally, the best performance of the model was chosen. Using SPSS 25.0 to analyze the data, P<0.05 was considered to be statistically significant. Results:The accuracy of the decision tree, support vector machine, random forests and extreme gradient boosting establish differential diagnosis model was 67.95%, 70.51%, 80.77% and 83.33%, respectively; AUC values was 0.74, 0.76, 0.80 and 0.83; Judgment for primary IgA nephropathy F1 score was 0.73, 0.72, 0.80 and 0.83, respectively. The efficiency of the extreme gradient boosting model based on the above evaluation indicators is the highest, its diagnosis of IgA nephropathy of the sensitivity and specificity respectively 89% and 79%. The variable importance from high to low was blood albumin, IgA/C3, serum creatinine, age, urine protein, urine albumin, high-density lipoprotein cholesterol, urea.Conclusion:The differential diagnosis model for IgA nephropathy was established successfully and non-IgA nephropathy and the efficiency performance of the extreme gradient boosting algorithm was the best.

Progress of IgA antibody class switch in the pathogenesis of IgA nephropathy / 国际儿科学杂志

IgA nephropathy(IgAN)is a common primary glomerular disease.The abnormal increase of IgA molecules in serum can be regarded as the initiation stage of IgAN development, and the abnormal IgA antibody class switch process in B cells leads to the overproduction of IgA.In order to provide new ideas for the prevention and treatment of IgAN, this paper reviews the role of IgA antibody class switch in the pathogenesis of IgAN from the aspects of mucosal immunity, T cells, cytokines and signaling pathways, as well as possible therapeutic targets.

Correlation between serum cystatin C level and clinicopathological features of IgA nephropathy / 中华检验医学杂志

Objective:To investigate the correlation between serum cystatin C (CysC) and clinical and pathological features of IgA nephropathy.Methods:Four hundred and twenty-one cases of primary IgA nephropathy diagnosed by renal biopsy in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2010 to January 2021 were retrospectively analyzed. According to the serum CysC level at the time of renal biopsy, the patients were divided into high serum CysC group and normal serum CysC group, and the clinical data and pathological indices of the patients were compared. Spearman correlation analysis was used to analyze the correlation between estimated glomerular filtration rate (eGFR) and serum CysC. The clinicopathological factors related to the serum CysC level were analyzed by multiple linear regression. The area under the receiver operator characteristic curve (AUC) was used to evaluate the ability of serum CysC level to predict related pathological injury.Results:The age, prevalence of hypertension, serum creatinine, urea and uric acid levels of high serum CysC group were significantly higher than those of normal serum CysC group, while the eGFR level was significantly lower than that of normal serum CysC group ( P<0.05). Spearman correlation analysis showed that serum CysC was negatively correlated with eGFR ( r=-0.744, P<0.001). In terms of pathological injury, the degree of renal tubular atrophy and renal interstitial fibrosis (T) and renal arteriole wall thickening (A) in high serum CysC group were more serious than those in normal serum CysC group ( P<0.05). Multiple linear regression analysis showed that the prevalence of hypertension, serum creatinine, urea, uric acid, T and A were correlated with serum CysC levels (standard regression coefficient β=0.048, 0.299, 0.260, 0.134, 0.195, 0.068, respectively, P<0.05). After adding serum CysC on the basis of clinical features, the prediction efficiency of renal tubular atrophy and renal interstitial fibrosis was higher (AUC were 0.829 [95% CI 0.787-0.870], 0.847 [95% CI 0.808-0.886], P<0.05). Conclusions:Patients with older age, hypertension, poor renal function and severe pathological damage are more likely to have elevated serum CysC levels. Serum CysC was related to the prevalence of hypertension, creatinine, urea, uric acid, T and A. Combined with serum CysC level can effectively improve the ability prediction of T.