Analysis of 111 cases of aristolochic acids nephropathy / 药学实践杂志

Objective To analyze the clinical characteristics and regularity of aristolochic acid nephropathy (AAN) induced by drugs containing aristolochic acid. Methods The clinical data of 111 patients with AAN induced by aristolochic acid were reviewed. The clinical features, medication and treatment of AAN were analyzed. Results Among 111 patients, there were more females than males (2.58∶1), 101 cases (90.99%) were over 50 years old； the mean age was (63.70±11.67) years old;the average duration of medication was (8.08±6.94) years. The drugs involved were Guanxinsuhe pill and Longdanxiegan pill in 106 cases (95.50%). Serum creatinine increased in 108 cases, urea nitrogen increased in 106 cases and hemoglobin decreased in 103 cases, most of which were hypogravity urine, mild to moderate proteinuria and occult blood. Ultrasonic examination revealed that the kidneys were damaged to varying degrees. Pathological biopsy of kidney showed renal tubular damage. Most patients had an insidious onset and varying degrees of progression, which were not proportional to the age and the duration of taking the medicine. In clinical, the renal function was progressively damaged, most of which were irreversible and with a poor prognosis. Conclusion Patients with renal impairment differed greatly individually, and the renal damage was not paralleled with the medication duration and dose of drugs containing aristolochic acid.AAN progressed rapidly, and the disease still progressed even after stopping taking drugs containing aristolochic acid. Strengthening pharmacovigilance, implementing early diagnosis and effective intervention could help to reduce the occurrence of AAN and attenuate its development.

Anti-C1q como Marcador de Nefritis Lúpica / Anti-C1q as Lupus Nephritis Marker

Introducción: Los autoanticuerpos anti-C1q han sido propuestos como un marcador útil en el lupus eritematoso sistémico por su asociación con la nefritis lúpica. Objetivo: Determinar la prevalencia de anti-C1q en pacientes con lupus eritematoso sistémico y otras enfermedades reumáticas para la evaluar la asociación con la nefropatía lúpica. Métodos: Se incluyeron 179 pacientes con lupus eritematoso sistémico y 82 con otras enfermedades reumáticas. La nefritis lúpica fue diagnosticada en 70 (39 por ciento) de los pacientes con lupus eritematoso sistémico. Los anticuerpos anti-C1q IgG se determinaron por ELISA. Las asociaciones se evaluaron por análisis de regresión logística. Resultados: La prevalencia de anti-C1q fue de 37 poe ciento (66/179) en los pacientes con lupus eritematoso sistémico y de 9 por ciento (7/82) en controles (OR = 6,3; IC 95 por ciento 2,8-14,1; p < 0,001). El anti-C1q fue asociado con proteinuria (OR = 2,6; IC 95 por ciento 1,2-6,0; p < 0,022); eritrosedimentación elevada (OR = 3,2; IC 95 por ciento 1,5-6,7; p < 0,003) y anti-DNAdc (OR = 3,9; IC 95 por ciento 1,7-9,1; p < 0,002). En el modelo de regresión logística ajustado para demografía y anti-DNAdc, aunque la OR del anti-C1q para la nefritis fue 2 veces más alta que en ausencia del anti-C1q, solo se aproximó a la significación estadística. La positividad simultánea de anti-C1q y anti-DNAdc estuvo asociada a la nefritis lúpica (OR = 4,3; IC 95 por ciento 1,9-9,5; p < 0,001). Conclusiones: El anti-C1q se presentó con mayor frecuencia en pacientes con lupus eritematoso sistémico que en los controles. El anti-C1q combinado con anti-DNAdc resultó fuertemente asociado a la nefritis lúpica(AU)

Introducción: Anti-C1q autoantibodies have been proposed as useful marker in systemic lupus erythematosus due to their association with lupus nephritis. Objective: To determine the prevalence of anti-C1q in patients with systemic lupus erythematosus and other rheumatic diseases to evaluate the association with lupus nephropathy. Methods: One hundred seventy-nine patients with systemic lupus erythematosus and 82 with other rheumatic diseases were included. Lupus nephritis was diagnosed in 70 (39percent) of patients with systemic lupus erythematosus. Anti-C1q IgG antibodies were determined by ELISA. Associations were evaluated by logistic regression analysis. Results: The prevalence of anti-C1q was 37percent (66/179) in patients with systemic lupus erythematosus and 9percent (7/82) in controls (OR = 6.3; 95percent CI 2.8-14). .1; p < 0.001). Anti-C1q was associated with proteinuria (OR = 2.6; 95percent CI 1.2-6.0; p < 0.022); elevated erythrocyte sedimentation rate (OR = 3.2; 95percent CI 1.5-6.7; p < 0.003) and anti-dsDNA (OR = 3.9; 95percent CI 1.7-9.1; p < 0.002). In the logistic regression model adjusted for demographics and anti-dsDNA, although the OR of anti-C1q for nephritis was 2-fold higher than in the absence of anti-C1q, it only approached statistical significance. Simultaneous positivity of anti-C1q and anti-dsDNA was associated with lupus nephritis (OR = 4.3; 95percent CI 1.9-9.5; p < 0.001). Conclusions: Anti-C1q occurred more frequently in patients with systemic lupus erythematosus than in controls. Anti-C1q combined with anti-dsDNA was strongly associated with lupus nephritis(AU)

Kidney Disease in Ankylosing Spondylitis: a case series and review of the literature / Doença Renal na Espondilite Anquilosante: uma série de casos e revisão da literatura

Abstract Background Kidney disease is a rare manifestation of ankylosing spondylitis (AS) and its pathological alterations remain poorly described. The aim of this study was to investigate the clinical presentation and pathological alterations on kidney biopsy of AS patients and review and discuss the current literature on the issue. Methods: We retrospectively studied the clinical presentation and kidney pathological alterations of 15 Caucasian AS patients submitted to kidney biopsy between October 1985 and March 2021. Results: Patients were predominantly male (66.7%) with median age at the time of kideney biopsy of 47 years [IQR 34 - 62]. Median serum creatinine at presentation was 1.3 mg/dL [IQR 0.9 - 3] and most patients also had either proteinuria (85.7%) and/or hematuria (42.8%). The most common indication for kidney biopsy was nephrotic syndrome (33.3%), followed by acute or rapidly progressive kidney injury (20%) and chronic kidney disease of unknown etiology (20%). Chronic interstitial nephritis (CIN) (n=3) and AA amyloidosis (n=3) were the most common diagnosis. Others included IgA nephropathy (IgAN) (n=2), focal segmental glomerulosclerosis (n=2), membranous nephropathy (n=1), and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN)(n=1). Conclusions: We present one of the largest series of biopsy-proven kidney disease in Caucasian AS patients. We found a lower prevalence of IgAN than previously reported in Asian cohorts. We found a higher prevalence of CIN and a lower prevalence of AA amyloidosis than that described in previous series of Caucasian patients. We also present the first case of AS-associated IC-MPGN.

Resumo Antecedentes: A doença renal é uma manifestação rara de espondilite anquilosante (EA) e as suas alterações patológicas permanecem pouco descritas. O objetivo deste estudo foi investigar a apresentação clínica e alterações patológicas na biópsia renal de doentes com EA bem como rever e discutir a literatura atual sobre o assunto. Métodos: Estudamos retrospectivamente a apresentação clínica e alterações patológicas renais de 15 doentes caucasianos com EA submetidos a biópsia renal entre Outubro de 1985 e Março de 2021. Resultados: Os doentes eram predominantemente homens (66,7%) com idade mediana no momento da biópsia de 47 anos [IIQ 34 - 62]. A creatinina sérica mediana na apresentação foi de 1,3 mg/dL [IIQ 0,9 - 3] e a maioria dos pacientes apresentava também proteinúria (85,7%) e/ou hematúria (42,8%). A indicação mais comum para biópsia renal foi a síndrome nefrótica (33,3%), seguida de lesão renal aguda ou rapidamente progressiva (20%) e doença renal crónica de etiologia desconhecida (20%). A Nefrite intersticial crónica (NIC) (n=3) e a amiloidose AA (n=3) foram os diagnósticos mais comuns. Outros incluíram nefropatia por IgA (NIgA) (n=2), glomeruloesclerose segmentar focal (n=2), nefropatia membranosa (n=1) e glomerulonefrite membranoproliferativa mediada por imunocomplexos (GNMP-IC) (n=1). Conclusões: Apresentamos uma das maiores séries de doenças renais comprovadas por biópsia em doentes caucasianos com EA. Encontramos uma prevalência de NIgA menor do que a relatada anteriormente em coortes asiáticas. Encontramos uma maior prevalência de NIC e uma prevalência menor de amiloidose AA do que a descrita em séries anteriores de pacientes caucasianos. Também apresentamos o primeiro caso de GNMP-IC associada à EA.

Renal-limited systemic lupus erythematosus: Avoiding delay in diagnosis

Nephrotic syndrome (NS) and glomerulonephritis (GN) are disorders of varied etiologies. Systemic lupus erythematosus (SLE) is one of the multisystemic diseases causing NS and GN. SLE is often suspected whenever NS/GN is associated with extrarenal manifestations. However, it presents solely as NS or GN without extrarenal features in a handful of cases. This affects the prognosis adversely as negligent delay in diagnosis of SLE and initiation of immunosuppressive therapy is associated with poorer response. We present a series of five women who presented solely with renal manifestations. The diagnosis of SLE was delayed, as the women did not have any extrarenal features. We started immunosuppressive therapy after a diagnosis of lupus nephritis was made in retrospect after a kidney biopsy. This case series highlights the importance of performing serology tests for SLE in all young female patients who present with NS/GN to avoid delay in diagnosis.

Clinical value of combined detection of serum IgG, TBX21 and miR-335 in diagnosis of lupus nephritis / 国际生物医学工程杂志

Objective:To investigate the clinical value of combined detection of serum immunoglobulin G (IgG), T-frame protein 21 (TBX21), and microRNA-335 (miR-335) in the diagnosis of lupus nephritis (LN).Methods:Ninety-five patients with LN treated in our hospital from January 2021 to January 2023 were selected as the observation group, while ninety-five healthy individuals were selected as the control group. Based on the systemic lupus erythematosus disease activity index (SLEDAI) score at admission, the LN patients were divided into two subgroups: the active LN group (51 cases, SLEDAI score > 4) and the stable LN group (44 cases, SLEDAI score = 0 - 4). The levels of serum IgG, TBX21, and miR-335 were compared between the two groups, and the levels of serum IgG, TBX21, miR-335, blood urea nitrogen (BUN), serum creatinine (Scr), complement C3, complement C4, and SLEDAI score were compared between the two groups. The correlations of serum IgG, PTX3, and miR-335 levels with BUN, Scr, complement C3, complement C4, and SLEDAI scores were analyzed. The diagnostic value of serum IgG, TBX21, and miR-335 in LN was evaluated.Results:Compared with the control group, the levels of serum IgG, TBX21, and miR-335 in the observation group were higher on admission (all P < 0.05). The serum levels of IgG, TBX21, and miR-335 in patients with the active stage were higher than those in patients with the stable stage on admission (all P < 0.05). On admission, the BUN, Scr, and SLEDAI scores of patients in the active stage were higher than those in the stable stage, and the levels of complement C3 and C4 were lower than those in the stable stage (all P < 0.05). The levels of serum IgG, TBX21, and miR-335 on admission were positively correlated with BUN, Scr, and SLEDAI scores and negatively correlated with complement C3 and C4 levels (all P < 0.05). The area under the curve (AUC) of the combination of serum IgG, TBX21, and miR-335 levels in the diagnosis of LN was greater than that of single detection ( P < 0.05). Conclusions:Serum IgG, TBX21, and miR-335 are closely related to disease activity and can be used as reference indicators for the diagnosis and prediction of LN in clinical practice, enabling the development of early targeted treatment plans.

Belimumabe comparado à terapia padrão do Sistema Único de Saúde no tratamento da nefrite lúpica nos estágios III, IV e V: revisão rápida / Belimumab compared to standard therapy of the Brazilian Public Health System in the treatment of lupus nephritis in stage III, IV, and V: rapid review

Belimumabe, rituximabe, terapia imunossupressora. Indicação: Nefrite lúpica nos estágios III, IV, V, refratária à terapia imunossupressora. Pergunta: Belimumabe é eficaz (remissão da nefrite, normalização da perda da função renal, qualidade de vida) e seguro (descontinuação devido a eventos adversos totais e eventos adversos graves) para o tratamento de pacientes com nefrite lúpica refratária nos estágios III, IV, V em comparação aos medicamentos disponíveis no Sistema Único de Saúde? Objetivo: Avaliar a segurança e eficácia do belimumabe em comparação com os medicamentos disponíveis no Sistema Único de Saúde em pacientes adultos com nefrite lúpica. Métodos: Revisão rápida de revisões sistemáticas. Levantamento bibliográfico foi realizado nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library e em registros de revisões sistemáticas e ensaios clínicos. Seguiu estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica dos estudos incluídos através da ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Foram selecionadas duas revisões sistemáticas que atendiam aos critérios de elegibilidade, mas nenhum ensaio clínico foi escolhido, pois não atendiam aos critérios de inclusão. Conclusão: a terapia combinada de belimumabe, ou de rituximabe, com tratamento imunossupressor padrão é mais eficaz que o tratamento padrão para alcançar remissão clínica da nefrite lúpica. A terapia combinada é tão segura quanto o tratamento padrão. Belimumabe e rituximabe tem eficácia similar entre si

Belimumab, rituximab, and immunosuppressive therapy. Indication: Refractory lupus nephritis to immunosuppressive therapy in stages III, IV, V. Question: Is belimumab effective (for remission of nephritis, normalization of loss of renal function, quality of life) and safe (for discontinuation due to total adverse events and serious adverse events) in the treatment of patients with refractory lupus nephritis in stages III, IV, V compared to the drugs available in the Brazilian Public Health System? Objective: To evaluate the safety and efficacy of belimumab compared to drugs available in the Brazilian Public Health System in adult patients with lupus nephritis. Methods: Rapid review of systematic reviews. A bibliographic search was done in the PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library databases and in records of systematic reviews and clinical trials. It has followed predefined search strategies. The methodological quality of the included studies was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: Two systematic reviews were selected, which met the eligibility criteria, but no clinical trials were chosen, as they did not meet the inclusion criteria. Conclusion: Combination therapy of belimumab or rituximab with standard immunosuppressive treatment is more effective than standard treatment in achieving clinical remission of lupus nephritis. Combination therapy is as safe as standard treatment. Belimumab and rituximab have similar efficacy to each other

Hipoacusia Neurosensorial en el síndrome de Alport: Una revisión Sistemática / Sensorineural hearing loss in Alport syndrome: A systematic review

El Síndrome de Alport (SA) es un desorden genético originado por mutaciones en el colágeno tipo IV que es el constituyente principal de las membranas basales. Clínicamente, se caracteriza por nefropatía hereditaria progresiva. En el oído interno, el colágeno IV se encuentra ubicado en la membrana basilar y en el ligamento espiral, por lo que las mutaciones en los genes codificadores provocan hipoacusia de tipo neurosensorial. La presente investigación tiene por objetivo caracterizar el comportamiento de la pérdida de audición en personas diagnosticadas con SA, mediante la revisión de estudios de la literatura. Se realizó una búsqueda en bases de datos con los criterios de inclusión establecidos, incorporando un total de siete artículos para su análisis. Teniendo en cuenta los hallazgos de las diversas investigaciones recopiladas, se concluye que la pérdida auditiva secundaria al SA es heterogénea. No hay un patrón común de presentación pues depende del modo de herencia y del tipo de mutación de la enfermedad, además su grado de severidad y progresión va paralelo a la función renal. Sin embargo, independientemente del momento en que se manifieste el deterioro auditivo, es de vital importancia una intervención audiológica oportuna, con el fin de detectar la hipoacusia lo más temprano posible, hacer un seguimiento riguroso de la funcionalidad auditiva y, en caso de ser necesario, adaptar ayudas auditivas de acuerdo con las necesidades comunicativas del paciente

Alport Syndrome (AS) is a genetic disorder originated by mutations in the collagen type IV which is the main constituent of the basal membranes. Clinically, is characterized by progressive hereditary nephropathy. In the inner ear, the collagen IV is ubicated in the basilar membrane and in the spiral ligament, whereby the mutations in the codifier gens, cause neurosensorial hearing loss. The aim of this investigation is to characterize how hearing loss behaves in people diagnosed with AS, by presenting a reviewing of reported studies in the literature. A database search was performed with the established criteria of inclusion and a total of seven articles were incorporated for its analysis. Considering the findings by the several investigations collected the conclusion is that the secondary hearing loss to AS is heterogenous. There is no a common pattern of presentation as it depends on the mode of heredity and the type of mutation of the disease, and besides of the degree of severity and progression that goes along with the renal function. Nevertheless, regardless of the moment that the auditive impair appears, it is of vital importance an opportune audiological intervention, aiming at detecting an alteration as soon as possible, make a rigorous tracking of the auditive functionality and, if necessary, incorporate hearing aids in accordance with the communicative needs of the patients

Cell phenotypes as activity biomarkers in patients with Systemic Lupus Erythematosus

Abstract The pathogenesis of systemic lupus erythematosus (SLE) is complex. Few studies in Brazilian population have addressed cell phenotypes associated with immunological responses and their associations with SLE activity. The aim of this study is to investigate cell phenotypes associated to SLE diagnosis, treatment and activity. Twenty-eight SLE female patients (17 inactive, 11 active) and 10 healthy women were included in this study. Markers of natural killer (Nk), T and B cells in peripheral blood were evaluated by flow cytometry. Nkt cells were decreased only in SLE active patients. Activated CD4+, regulatory T FoxP3+ and B cells were decreased in both active and inactive SLE patients, compared to control group. The data corroborate the disruption of immune regulatory response in SLE patients and suggest phenotipic changes as possible biomarkers of SLE activity.

Clinical Efficacy of Niaoxue No.1 Prescription in Treatment of Henoch-Schönlein Purpura Nephritis with Blood Heat and Stasis Syndrome in Children / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Niaoxue No.1 Prescription in treating Henoch-Schönlein purpura （HSP） nephritis with blood heat and stasis syndrome and its effect on urine erythrocyte， urine protein， blood neutrophils， and blood routine-derived indicators. MethodA multicenter， randomized controlled trial （RCT） was conducted involving 108 HSP nephritis patients from three hospitals. The patients were randomly divided into a control group （54 cases） and a treatment group （54 cases）. The treatment group received Niaoxue No.1 prescription once daily， while the control group was treated with captopril and ferulic acid tablets. Both groups underwent a 4-week course of treatment. The urine erythrocyte， urine microalbumin （mAlb）， urine sediment red blood cell count， traditional Chinese medicine （TCM） syndrome score， 24-hour urine protein， blood neutrophil count， neutrophil to lymphocyte ratio （NLR）， platelet to lymphocyte ratio （PLR）， lymphocyte to monocyte ratio （LMR）， D-dimer， and immunoglobulin A were detected. The recurrence rate of HSP nephritis was followed up for 6 months. ResultThe total effective rates were 88.9% （48/54） in the treatment group and 70.4% （38/54） in the control group， and the treatment group was superior to the control group （χ2=5.708， P<0.05）. Compared with the results before treatment， after 14 days of treatment， the TCM syndrome total score， urine erythrocyte， urine mAlb， and 24-hour urine protein in both groups significantly decreased （P<0.05，P<0.01）， and the improvement was more significant in the treatment group than the control group （P<0.05）. After 28 days of treatment， compared with the results before treatment， the TCM syndrome total score， urine erythrocyte， urine mAlb， urine sediment red blood cell count， D-dimer， and 24-hour urine protein in both groups significantly decreased （P<0.05，P<0.01）， with the treatment group showing a more significant reduction in urine mAlb than the control group （P<0.05）. On the 14th and 28th days of treatment， the neutrophil percentage and NLR were lower in the treatment group than in the control group （P<0.05）， while there was no statistically significant difference in PLR and LMR. The recurrence rate of nephritis in both groups showed no statistically significant difference after a 6-month follow-up. ConclusionNiaoxue No.1 Prescription in the treatment of HSP nephritis with blood heat and stasis syndrome can significantly improve clinical symptoms， shorten the course of the disease， and reduce urine erythrocyte， urine mAlb， 24-hour urine protein， blood neutrophils， and NLR， thereby effectively alleviating the inflammatory state and reducing kidney damage in children with HSP nephritis.

Biologics in treatment of lupus nephritis / 中华肾脏病杂志

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes damage to multiple vital tissues and target organs, and lupus nephritis (LN) is a serious complication of SLE involving the kidneys. The use of glucocorticoids and immunosuppressants has been dominant in the treatment strategy of LN, while their adverse effects have also raised concerns. In recent years, the development and use of biologics have provided new ideas for the treatment of LN and have also achieved positive efficacy in several clinical trials in SLE and LN. Biologics can be divided into monoclonal antibodies and recombinant proteins, which exert therapeutic effects on SLE and LN through a variety of mechanisms at the cellular-molecular level. In this article, we review recent research advances in the treatment of SLE and LN from the perspective of the different mechanisms of action of biologics.

Fanconi syndrome secondary to primary biliary cholangitis: a case report / 中华肾脏病杂志

Primary biliary cirrhosis/cholangitis is an autoimmune disease. Renal tubular acidosis is a common form in PBC cases, but Fanconi syndrome is rarely reported. The paper reported a 66-year-old female patient with fatigue, renal insufficiency and elevated bile duct enzymes. The patient presented with type 2 proximal renal tubular acidosis and complete Fanconi syndrome. Laboratory examinations showed high-titer-positive anti-mitochondrial antibodies, elevated serum IgM, and type 3 cryoglobulinemia. Renal biopsy revealed interstitial nephritis, and electron micrographs showed abnormal mitochondria in proximal tubular epithelial cells. The patient's renal function ameliorated, and acid-base imbalance and electrolyte disturbances were corrected after high-dose glucocorticoid treatment.

Clinical characteristics and risk factors of acute focal bacterial nephritis in children / 中华肾脏病杂志

Objective:To summarize and analyze the clinical features and risk factors of acute focal bacterial nephritis (AFBN) in children.Methods:It was a retrospective cohort study. The clinical data of patients diagnosed with upper urinary tract infection in Children's Hospital Affiliated to Capital Institute of Pediatrics from July 1, 2016 to July 31, 2021 were collected, and the patients all received abdominal enhanced CT examination. According to the imaging examination results, the patients were divided into AFBN group and acute pyelonephritis (APN) group, and the clinical manifestations, laboratory and imaging examination between the two groups were compared. Logistic regression model and receiver operating characteristic curve were used to analyze the risk factors of AFBN.Results:A total of 135 patients with upper urinary tract infection were enrolled in this study, with age of 2.5 (0.5, 3.7) years old, and 68 males (50.4%). There were 67 patients (49.6%) in AFBN group and 68 patients (50.4%) in APN group. There were statistically significant differences in the highest fever temperature, duration of fever after treatment, proportion of lower urinary tract irritation symptoms, proportion of urinary tract malformation or abnormality, white blood cell count, neutrophil count, procalcitonin, C-reactive protein, proportion of pyuria, urinary β2 microglobulin and proportion of using carbapenem antibiotics between the two groups (all P<0.05). Multivariate logistic regression analysis result showed that urinary tract malformation/abnormality ( OR=3.34, 95% CI 1.23-9.10) and leukocytosis ( OR=1.25, 95% CI 1.03-1.51) were the independent risk factors of AFBN. Conclusions:The children with urinary tract infection who have high peak fever, long duration, obvious increase of inflammatory indexes and urinary β2 microglobulin may suggest AFBN. Urinary tract malformation/abnormality and high white blood cells are risk factors of AFBN.

Efficacy and safety of belimumab combined with standard regimen in the treatment of active lupus nephritis / 中华肾脏病杂志

Objective:To evaluate the efficacy and safety of belimumab combined with standard regimen in the treatment of active lupus nephritis (LN).Methods:It was a single-center, pre - and post-control retrospective study. The Data of active LN patients treated with belimumab combined with standard regimen in the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University from June 1, 2020 to June 30, 2022 were collected for analyzing the renal response rate and adverse reactions after belimumab treatment.Results:A total of 17 patients were included, including 14 females (82.35%). The age of the first medication was (26.06±2.64) years old, the median time of illness before the use of belimumab was 24.00 (8.50, 48.50) months, and the recurrence times before the use of belimumab was (1.24±1.03) times. All the 17 patients underwent renal biopsy. The main pathological types were type IV in 11 cases (11/17), type Ⅲ+V in 2 cases (2/17), type IV+V in 3 cases (3/17), and type V in 1 case (1/17). The dose of glucocorticoids was (22.95±8.30) mg/d in 1 year before belimumab administration. In 12 patients with LN who completed 24 weeks of belimumab treatment plan, the 24-hour urinary protein showed a downward trend, and there was a statistically significant difference compared with the baseline at 24 week [0.49 (0.15, 2.19) g vs. 2.83 (1.14, 4.11) g, Z=-2.100, P=0.036]. Compared with the baseline, serum albumin at 24 week increased by 29.36%, with statistically significant difference [(34.50±3.34) g/L vs. (26.67±5.75) g/L, t=-3.840, P=0.030]. The systemic lupus erythematosus disease activity index-2K score continued to decline, with statistically significant difference compared with baseline at 24 week (5.00±3.02 vs. 12.00±2.82, t=6.163, P<0.001). The lymphocyte count increased, and the difference was statistically significant compared with the baseline at 24 week [0.72(0.28, 2.39)×10 9/L vs. 0.30(0.19,0.34)×10 9/L, Z=-2.073, P=0.038]. There was a statistically significant difference between the glucocorticoids dosage at 24 week and the average glucocorticoids dosage 1 year before treatment [(11.25±6.35) mg/d vs. (22.60±9.75) mg/d, t=4.225, P=0.003]. After observation of belimumab for (38.13±22.93) weeks, patients had a complete response rate of 64.71% (11/17), a partial response rate of 17.65% (3/17), and an overall response rate of 82.35% (14/17). Relapse occurred in 1 case.No infusion-related reactions occurred in 17 patients. During the treatment, a total of 5 adverse events occurred, including 2 cases of pulmonary infection, 1 case each of sepsis, upper respiratory tract infection, and cytomegalovirus infection, which all improved after treatment and the subsequent treatment was not affected. Conclusion:Belimumab combined with standard regimen can improve the response rate of LN, reduce the recurrence rate, reduce the dosage of glucocorticoids, and control the overall adverse events with good prognosis.

Deciphering the pathogenicity of COL4A4 heterozygous splicing mutations and the genotype-phenotype correlation in autosomal dominant Alport syndrome / 中华肾脏病杂志

Objective:Through the investigation of the pathogenicity of COL4A4 heterozygous splicing mutations and the genotype-phenotype correlation in autosomal dominant Alport syndrome (ADAS), to better understand the impact of COL4A4 heterozygous splicing mutations on ADAS. Methods:The study was a case series analysis. Patients from 5 ADAS families with COL4A4 heterozygous splicing mutations detected by whole exome sequencing were recruited by three hospitals. In vivo transcriptional analysis and/or in vitro minigene splicing assay were conducted to determine the splicing patterns and assess the pathogenicity of COL4A4 heterozygous splicing mutations. Results:In the five ADAS pedigrees carrying COL4A4 heterozygous splicing mutations, four novel ADAS splicing patterns were described. In pedigree 1-4, most patients presented with continuous hematuria or/and microalbuminuria. Otherwise,the proband in pedigree 4 presented with macroalbuminuria and the proband in pedigree 1 had progressed to chronic kidney disease stage 2 at the age of 70 years old. In pedigree 5, all patients developed end-stage renal disease between 28 and 41 years old. c.735+3A>G detected in pedigree 1 and pedigree 2 and c.694-1G>C detected in pedigree 3 both led to exon 12 skipping in COL4A4, resulting in 42 nucleotides in-frame deletion (c.694_735del). c.2056+3A>G detected in pedigree 4 led to COL4A4 exon 26 skipping, which caused in-frame deletion of 69 nucleotides (c.1988_2056del). c.2716+5G>T detected in pedigree 5 led to a 360 nucleotides large in-frame deletion, including 100 bp sequence at the 3'end of exon 29,the whole sequence of exon 30 and 89 bp sequence at the 5'end of exon 31 (c.2446_2805del). Conclusions:Renal prognosis differs significantly for patients with small in-frame deletions versus large in-frame deletion splicing abnormalities. Determination of the pathogenicity and the splicing patterns of COL4A4 heterozygous splicing mutations using in vivo and in vitro transcriptional analysis may provide renal prognostic information.

Efficacy and safety of half-dose rituximab in the treatment of 23 cases with lupus nephritis / 中华内科杂志

The study aimed to analyze the efficacy and safety of rituximab in the treatment of 23 cases of lupus nephritis and explore the prospect of half-dose rituximab in lupus nephritis treatment. Twenty-three patients with lupus nephritis hospitalized in the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital from May 2013 to December 2021 were selected. Eighteen patients received rituximab 375 mg/m 2 on the first and 14th days, 5 patients received 500 mg of rituximab on the first and 14th days, and rituximab was used as needed 6 months later. Methylprednisolone (80-120 mg) was given together with rituximab. Afterward, 1 mg/kg prednisone was used for 4 weeks, which was progressively tapered to maintenance doses or discontinued. B lymphocyte level, renal function, 24-h urine protein level, and systemic lupus erythematosus (SLE) disease activity index 2000 (SLEDAI2K) score before and after treatment were recorded. The efficacy and adverse reactions were analyzed. The results showed that 11 patients suffered from renal insufficiency [creatinine (162.7±58.6) μmol/L ] at baseline, while the creatinine level of 9 patients returned to normal 12 months after the treatment [ (66.3±10.1)μmol/L ]. Normal renal function of the other 12 patients was maintained during treatment. After 12 months, the 24-h urine protein level decreased from 4.00 (2.00,6.80) g in the baseline period to 0.10 (0.08,0.40) g. SLEDAI2K score decreased from 22 (18,26) in the baseline period to 3 (0,6) 12 months after the treatment. The B lymphocyte level reached 0.00 (0.00,0.01)% at 3 months. Of 23 patients, 13 patients achieved complete remission, and 7 patients achieved partial remission after 6 months of rituximab treatment. Five patients experienced adverse reactions related to rituximab, including 1 case of transfusion reaction, 1 case of perioral herpes with pulmonary infection, and 3 cases of decreased IgG levels. Therefore, rituximab regimen used in this study can be an effective treatment strategy for lupus nephritis.

Role of light and immunofluorescence microscopy to differentiate primary and secondary membranous nephropathy

Context: Membranous nephropathy (MN) causes nephrotic syndrome, mostly primary but may be associated with SLE, infections, cancer, or drug. Aims: To estimate clinical, serological, light microscopic, and direct immunofluorescence (DIF) findings to differentiate primary and secondary MN. Settings and Design: Prospective, cross-sectional, single-center study in a tertiary care hospital. Methods and Material: Total 51 cases from September 2019 to February 2020. Laboratory Data: Blood glucose, urine analysis, urea, creatinine, albumin, cholesterol, HBsAg, Anti HCV, ASO, ANA, MPO ANCA, PR3 ANCA, dsDNA, PLA2R, C3, and C4. Clinical parameters: age, sex, BP, skin lesions, arthralgia, edema, obesity. Renal biopsies examined with H and E, PAS, silver methanamine, MT stains. DIF done with IgG, IgM, IgA, C3c, C1q, kappa, and lambda. Statistical Analysis Used: Statistical software (Graph Pad PRISM 6) and Chi-square test). Results: Among 51 cases, 25 are primary and 26 are secondary MN with 22 being lupus nephritis, with 2 being post-infectious and the remaining 2 being proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMIDD) with kappa chain restriction. Mean age was 37 ± 12.18 and 30.69 ± 13.92 years for primary and secondary MN, respectively. Significant male preponderance in primary MN. Serum C4 significantly low in secondary MN (15.34 ± 9.59). Microscopic hematuria present in secondary MN. Mesangial and endocapillary hypercellularity are significant in secondary MN. IgG and kappa are significantly intense in primary whereas IgA, C3c, and C1q are significantly intense in secondary MN. Conclusions: Reliable differentiation between primary and secondary MN has important therapeutic implications.

Clinical and immunological factors associated with lupus nephritis in an Argentine patient population: A cross-sectional study

Introduction: In recent decades, the prevalence of systemic lupus erythematosus (SLE) has increased thanks to early detection and the impact of new therapies on the survival of those affected. Up to 90% will have histopathological signs of kidney disease in the first 3 years of the disease, but lupus nephritis of clinical relevance will appear in 50% of cases, affecting kidney function and mortality. Despite aggressive therapeutic strategies, the prognosis of patients with LN remains unfavourable, mainly due to the high risk of progression to end-stage renal disease (10%-20%) and mortality from all causes. Objective: To describe the clinical and immunological risk factors of a group of patients with lupus, comparing clinical and serological characteristics in relation to renal involvement to establish possible associations. Materials and methods: Cross-sectional study in which 87 patients with SLE were included. Clinical and immunological variables were analyzed. Bivariate and multivariate analyses were performed using the presence of nephritis as an outcome. Results: The prevalence of lupus nephritis was 59%. The significantly associated variables were arterial hypertension (OR 3.1, 95% CI 1.02-9.40), age of onset of lupus less than 25 years (OR 2.7, 95% CI 1.08-6.73), the presence of reticular livedo (OR 4.1, 95% CI 1.09-15.7), positive anti-DNA (OR 2.9, 95% CI 1.18-7.24) and low levels of complement (OR 4.0, 95% CI 1.64-10.2). Conclusions: Urinary sediment abnormalities were the most common renal manifestation and lupus debut before the age of 25 seems to increase the risk of developing nephritis. Future research is required for a better explanation of the associations found.

Introducción: En las últimas décadas, la prevalencia del lupus eritematoso sistémico (LES) se ha incrementado gracias a la detección temprana y al impacto de las nuevas terapias en la sobrevida de los afectados. Hasta el 90% de ellos tendrá signos histopatológicos de afección renal en los primeros 3 arios de la enfermedad, pero la nefritis lúpica (NL) de relevancia clínica aparecerá en el 50% de los casos, afectando la función renal y la mortalidad. A pesar de las estrategias terapéuticas agresivas, el pronóstico de los pacientes con NL sigue siendo desfavorable, principalmente debido al alto riesgo de progresión a enfermedad renal crónica terminal (10-20%) y de mortalidad por todas las causas. Objetivo: Describir los factores de riesgo clínicos e inmunológicos de un grupo de pacientes con lupus, comparando características clínicas y serológicas en relación con el compromiso renal, a fin de establecer posibles asociaciones. Materiales y métodos: Estudio de corte transversal en el que se incluyeron 87 pacientes con LES. Se analizaron variables clínicas e inmunológicas. Los análisis bivariado y multivariados se realizaron utilizando la presencia de nefritis como desenlace. Resultados: La prevalencia de NL fue del 59%. Las variables asociadas significativamente fueron hipertensión arterial (OR: 3,1; IC 95%: 1,02-9,40), edad de aparición del lupus menor de 25 años (OR: 2,7; IC 95%: 1,08-6,73), presencia de livedo reticularis (OR: 4,1; IC 95%: 1,0915,7), anti-DNA positivo (OR: 2,9; IC 95%: 1,18-7,24) y niveles bajos de complemento (OR: 4,0; IC 95%: 1,64-10,2). Conclusiones: Las anormalidades en el sedimento urinario fueron la manifestación renal más común, en tanto que el inicio lúpico antes de los 25 años parece incrementar el riesgo de desarrollar nefritis. Se requieren futuras investigaciones que den una mejor explicación a las asociaciones encontradas.

Direct costs associated with lupus nephritis management in the Private Healthcare System in Brazil: an expert panel perspective / Custos diretos associados ao manejo da nefrite lúpica no Sistema de Saúde Privado no Brasil: uma perspectiva segundo painel de especialistas

Objective: To estimate direct medical costs of lupus nephritis (LN) in the Brazilian private healthcare system. Methods: An expert panel of five specialists were convened to discuss health resource usage in LN patient management. The discussion included diagnosis, treatment, and disease monitoring, including dialysis and kidney transplantation. Unit costs (in BRL) were obtained from public sources, and an estimation of 1-year costs was conducted. Results: Approximately 76.0% of patients with LN undergo kidney biopsy, of which 48.1% present with LN classes III­IV and 21.4% have class V. Around 67.5% of patients with LN classes III­IV experience an average of four renal flares annually. Overall, 20.3% of patients present refractory LN, and 10.3% have end-stage kidney disease (ESKD), requiring dialysis and kidney transplantation. Estimated total weighted annual costs per patient were BRL 115,824.81 for LN classes III­IV, BRL 85,684.79 for LN class V, BRL 115,594.98 for refractory LN; and BRL 325,712.88 for ESKD. The main annual cost driver for LN classes III­IV was renal flares (BRL 60,240.41; 52.0%) and dialysis for LN class V (BRL 31,128.38; 36.3%). Conclusions: Total direct costs increase when LN progresses to ESKD. Although it is challenging to improve the diagnosis, identification of the disease at an early stage, together with rapid initiation of treatment, are fundamental elements to optimize results, potentially reducing costs to the system and the impact of disease burden and quality of life on patients.

Objetivo: Estimar os custos médicos diretos da nefrite lúpica (NL) no sistema suplementar de saúde brasileiro. Métodos: Um painel de cinco especialistas foi estruturado para discutir o uso de recursos em saúde no manejo de pacientes com NL. Nesta discussão, incluíram-se o diagnóstico, o tratamento e o monitoramento da doença, contemplando também diálise e transplante renal. Os custos unitários foram obtidos de fontes públicas e os resultados expressos em custo anual. Resultados: Aproximadamente 76,0% dos pacientes com NL são submetidos à biópsia renal, sendo 48,1% com NL de classes III-IV e 21,4% de classe V. Cerca de 67,5% dos pacientes com classes III-IV apresentam, aproximadamente, quatro flares renais anuais. No geral, 20,3% dos pacientes apresentam NL refratária e 10,3% desenvolvem doença renal terminal (DRT), necessitando de diálise e transplante renal. O custo ponderado anual estimado por paciente foi de R$ 115.824,81 para NL de classes III-IV, R$ 85.684,79 para classe V, R$ 115.594,98 para NL refratária e R$ 325.712,88 para DRT. O principal fator para incremento dos custos anuais para NL de classes III-IV foram os flares renais (R$ 60.240,41; 52,0%) e, na classe V, a diálise (R$ 31.128,38; 36,3%). Conclusões: Há um incremento dos custos diretos da NL na progressão para DRT. Embora seja desafiador melhorar o diagnóstico, a identificação da doença em uma fase precoce, aliada ao tratamento iniciado de forma célere, são elementos fundamentais para otimizar os resultados, potencialmente reduzindo os custos ao sistema e o impacto da carga da doença e qualidade de vida dos pacientes.

Evaluation of herpesvirus members on hospital admission in patients with systemic lupus erythematous shows higher frequency of Epstein-Barr virus and its associated renal dysfunction / Avaliação de membros da família Herpesviridae na admissão hospitalar de pacientes com lúpus eritematoso sistêmico mostra maior frequência do vírus Epstein-Barr e sua disfunção renal associada

Abstract Introduction: Members of the Herpesviridae family have been described in patients with systemic lupus erythematous (SLE), but the clinical impact on renal function is not well known. Methods: HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8 were evaluated by molecular biology on admission in blood samples from 40 consecutive SLE patients hospitalized for lupus activity. Results: Patients were 90.0% female, 77.5% non-white, with average age of 32.7 ± 13.6 years. We found positivity for EBV (65.0%), CMV (30.0%), HSV-1 (30.0%), HHV-6 (12.5%), and HHV-7 (7.5%). For all viruses, age, SLEDAI, hematological tests, ferritin, LDH, C-reactive protein, and erythrocyte sedimentation rate (ESR) were not significant. However, EBV positivity was a significant factor for higher serum creatinine (3.0 ± 2.8 vs. 0.9 ± 0.8; P = 0.001) and urea (86 ± 51 vs. 50 ± 46; P = 0.03). Moreover, positive cases for EBV only or with combined co-infections (66.7%-CMV; 58.3%-HSV-1) or negative for EBV only were evaluated by Kruskal-Wallis test again showed statistical significance for serum creatinine and urea (both P ≤ 0.01), with posttest also showing statistical differences for renal dysfunction and EBV presence (alone or in combined co-infections). The presence of EBV viral load was also significant for nephrotic-range proteinuria, renal flare, and the need for hemodialysis. Conclusion: Members of the Herpeviridae family (mainly EBV, HSV-1 and CMV) are common on hospital admission of SLE patients, reaching 65% for EBV, which seems to be associated with renal dysfunction and could reflect a previous association or overlapping disease, which is not well understood.

Resumo Introdução: Membros da família Herpesviridae tem sido descritos em pacientes com lúpus eritematoso sistêmico (LES), mas o impacto clínico na função renal não é bem conhecido. Métodos: Avaliou-se HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8 por biologia molecular na admissão em amostras sanguíneas de 40 pacientes com LES consecutivos hospitalizados por atividade lúpica. Resultados: Pacientes 90,0% mulheres, 77,5% não brancos, idade média 32,7 ± 13,6 anos. Encontramos positividade para EBV (65,0%), CMV (30,0%), HSV-1 (30,0%), HHV-6 (12,5%), HHV-7 (7,5%). Para todos os vírus, idade, SLEDAI, exames hematológicos, ferritina, LDH, proteína C reativa, velocidade de hemossedimentação não foram significativos. Entretanto, positividade para EBV foi estatisticamente significativo para creatinina (3,0 ± 2,8 vs. 0,9 ± 0,8; P = 0,001) e ureia (86 ± 51 vs. 50 ± 46; P = 0,03) séricas mais elevadas. Ademais, casos positivos para EBV isolado ou com coinfecções combinadas (66,7%-CMV; 58,3%-HSV-1) ou negativos apenas para EBV foram avaliados pelo teste Kruskal-Wallis e novamente mostraram significância estatística para creatinina e ureia séricas (ambas P ≤ 0,01), com pós-teste mostrando também diferenças estatísticas para disfunção renal e presença de EBV (sozinho ou em coinfecções combinadas). A presença de carga viral do EBV também foi significativa para proteinúria de faixa nefrótica, inflamação aguda, necessidade de hemodiálise. Conclusão: Membros da família Herpeviridae (principalmente EBV, HSV-1, CMV) são comuns na admissão de pacientes com LES, chegando a 65% para EBV, que parece associar-se à disfunção renal podendo refletir associação prévia ou doença sobreposta, o que não é bem compreendido.