Clinicopathological characteristics and predictors of outcome of rapidly progressive glomerulonephritis: a retrospective study.

BACKGROUND: Globally, there are regional and time-based variations in the prevalence, etiology, and prognosis of rapidly progressive glomerulonephritis (RPGN). Prognosis of RPGN is poor, with a higher risk of death and end stage renal disease (ESRD) even with immunosuppressive medications. In the Middle East and North Africa, the studies on this disease are very limited. Therefore, we determined the predictors of outcome of RPGN. METHODS: We retrospectively assessed 101 adult patients over age of 18, diagnosed with RPGN based on renal biopsy illustrating crescents in ≥ 50% of the glomeruli. Patients who had crescents in their renal biopsies that were < 50% and those who refused to consent to a renal biopsy were excluded. We categorized the patients into 3 groups based on immunohistochemistry; type I, type II and type III. Then, depending on renal loss, we divided them into ESRD and non-ESRD groups. The clinical history and physical examination were retrieved. Additionally, 24-hour urine protein, urine analysis, renal function tests, serum albumin, complete blood count, antinuclear antibodies, anti-double stranded DNA antibodies, ANCA antibodies and serum complement levels were checked. Each patient underwent a kidney biopsy for immunohistochemistry and light microscopy. The percentage of crescentic glomeruli, number of sclerosed glomeruli, tertiary lymphoid organ (TLO), neutrophil infiltration, endocapillary or mesangial hypercellularity, interstitial fibrosis with tubular atrophy (IFTA) were analyzed. Primary outcomes (remission, ESRD and mortality) and secondary outcomes were assessed. RESULTS: Type II was the most frequent cause of RPGN (47.5%), followed by type III (32.7%) and type I (19.8%). 32 patients (31.7%) died during follow up, whereas 60 patients (59.4%) developed ESRD. In 41 patients (40.6%), remission occurred. Oliguria, serum creatinine, and need for HD at presentation were significantly increased in ESRD group compared to non-ESRD group (P < 0.001 for each). Mesangial proliferation, IFTA, TLO formation, sclerotic glomeruli and fibrous crescents were also significantly increased in ESRD group in comparison to non-ESRD group (P < 0.001 for each). Glomerulosclerosis (P = 0.036), and IFTA (P = 0.008) were predictors of ESRD. Infections (P = 0.02), respiratory failure (P < 0.001), and heart failure (P = 0.004) were mortality risk factors. CONCLUSION: Type II RPGN was the most common. Infection was the most frequent secondary outcome. Oliguria, glomerulosclerosis, the requirement for hemodialysis at presentation, IFTA and TLO formation were predictors of ESRD. Respiratory failure, heart failure and infections were significant predictors of mortality.

Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis.

BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. METHODS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. RESULTS: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. CONCLUSIONS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

Seasonal patterns of toxicity in melanoma patients treated with combination anti-PD-1 and anti-CTLA-4 immunotherapy.

BACKGROUND: Immune checkpoint inhibitors are frequently associated with the development of immunotherapy-related adverse events (irAEs). The exact etiology, including the role of environmental factors, remains incompletely understood. METHODS: We analyzed the records of 394 melanoma patients from three centers (northern and southern hemisphere). Patients had received at least one cycle of anti-PD-1/anti-CTLA-4 with a minimum follow-up of 3 months. We study the distribution and time to irAEs onset throughout the calendar year. RESULTS: 764 irAEs were recorded; the most frequent were skin rash (35%), hepatitis (32%) and colitis (30%). The irAEs incidence was the highest in autumn and winter, and the ratio for the 'number of irAEs' per 'therapies commenced' was the highest in winter and lowest in summer (2.4 and 1.7, respectively). Season-specific patterns in the time of irAEs onset were observed for pneumonitis (shorter time to onset in autumn, p = 0.025), hepatitis (shorter time to onset in spring, p = 0.016) and sarcoid-like immune reaction (shorter time to onset in autumn, p = 0.041). Season-specific patterns for early-onset irAEs were observed for hepatitis (spring, p = 0.023) and nephritis (summer, p = 0.017). Early-onset pneumonitis was more frequent in autumn-winter (p = 0.008) and early-onset nephritis in spring-summer (p = 0.004). CONCLUSIONS: Environmental factors that are associated with particular seasons may contribute to the development of certain irAEs and suggest the potential effect of environmental triggers. The identification of these factors may enhance preventive and therapeutic strategies to reduce the morbidity of irAEs.

A systematic review and meta-analysis of mortality and kidney function in uranium-exposed individuals.

BACKGROUND: Humans are exposed to uranium (U) in a variety of applications. Both animal and observational human studies support an associated U nephrotoxicity. Few statistical syntheses of the human data have been performed and these analyses are limited in the types of exposures considered. OBJECTIVES: This study aims to evaluate the state of current evidence and to expand on existing meta-analyses by systematically evaluating kidney-associated causes of mortality in multiple U-exposed populations. This study also aims to evaluate the effect of U exposure on kidney function and biomarkers of kidney injury. METHODS: The published and grey literature were systematically reviewed for studies that reported Standardized Mortality Ratios (SMR) for kidney cancer, chronic nephritis/nephrosis, all-cause mortality, diabetes, all circulatory/heart disease, and/or ischemic heart disease in U-exposed humans. Studies that reported kidney biomarker measures for U-exposed versus control subjects were identified separately. RESULTS: 36 studies were included. The studies were parsed into subgroups based on setting of exposure. Analysis of kidney cancer and chronic nephritis/nephrosis mortality demonstrated an SMR of 0.93 (95CI: 0.82-1.05) and 0.82 (95CI: 0.70-0.96), respectively. The other clinical outcomes evaluated also demonstrated mortality deficits in exposed relative to unexposed individuals. Subgroup analyses demonstrated similar mortality deficits. Conversely, biomarker analyses suggested better kidney function in the controls, but none of these differences reached significance. DISCUSSION: Given that most of the included mortality studies were conducted in occupational populations, the mortality deficits observed in our analyses were likely due to the healthy-worker effect. Additionally, our analyses of kidney biomarkers were severely limited by low precision due to a low number of available studies and small study-size. Future work needs to evaluate the progression of chronic and to end-stage kidney disease in community-based populations to better assess the full impact of prolonged chronic U exposure on kidney outcomes.

A case of rapidly progressive glomerulonephritis with double-positive anti-GBM antibody and MPO-ANCA after SARS-CoV-2 vaccination and relapse during 1 year follow-up.

Although mRNA vaccines for COVID-19 are highly beneficial and are recommended for patients with kidney disease, adverse reactions in some patients after vaccination have been problematic. Various vasculitis and renal disorders have been reported after vaccination; however, a causal relationship has not yet been identified. In this report, we describe a case of rapidly progressive glomerulonephritis that developed after SARS-CoV-2 vaccination, in which both anti-glomerular basement membrane (anti-GBM) and myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) were present. The patient's renal biopsy showed that of the 48 glomeruli in total, four showed global sclerosis and none showed segmental sclerosis. The biopsy showed 11 cellular glomerular crescents and 5 fibrocellular glomerular crescents. Renal function improved with steroids, rituximab, and plasma exchange. Approximately 9 months later, MPO-ANCA was again elevated, and the pulmonary lesions worsened, again requiring multidisciplinary treatment. This case suggests that caution should be exercised in the development of double-positive disease after vaccination, and that long-term observation may be necessary because of the possibility of relapse.

[Therapeutic effect of mycophenolate mofetil or cyclophosphamide in children with Henoch-Schönlein purpura nephritis of different age groups]. / ä¸åŒå¹´é¾„æ®µè¿‡æ•æ€§ç´«ç™œæ€§è‚¾ç‚Žæ‚£å„¿æŽ¥å—éœ‰é šé ¸é ¯æˆ–çŽ¯ç£·é °èƒºæ²»ç–—çš„ç–—æ•ˆå·®å¼‚åˆ†æž.

OBJECTIVES: To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups. METHODS: A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (n=30), the >12 years MMF subgroup (n=15), the ≤12 years CTX subgroup (n=71), and the >12 years CTX subgroup (n=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions. RESULTS: There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (P>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (P>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (P<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (P<0.05). CONCLUSIONS: The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.

Review on Molecular Mechanism of Hypertensive Nephropathy.

Hypertension, a prevalent chronic ailment, has the potential to impair kidney function, and thereby resulting in hypertensive nephropathy. The escalating incidence of hypertensive nephropathy attributed to the aging population in urban areas, has emerged as a prominent cause of end-stage renal disease. Nevertheless, the intricate pathogenesis of hypertensive nephropathy poses considerable obstacles in terms of precise clinical diagnosis and treatment. This paper aims to consolidate the research findings on the pathogenesis of hypertensive nephropathy by focusing on the perspective of molecular biology.

Dapagliflozin alleviates renal inflammation and protects against diabetic kidney diseases, both dependent and independent of blood glucose levels.

Introduction: Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide. Therefore, efforts to understand DKD pathophysiology and prevent its development at the early phase are highly warranted. Methods: Here, we analyzed kidneys from healthy mice, diabetic mice, and diabetic mice treated with the sodium-glucose cotransporter 2 inhibitor dapagliflozin using ATAC and RNA sequencing. The findings were verified at the protein levels and in cultured cells. Results: Our combined method of ATAC and RNA sequencing revealed Csf2rb, Btla, and Isg15 as the key candidate genes associated with hyperglycemia, azotemia, and albuminuria. Their protein levels were altered together with multiple other inflammatory cytokines in the diabetic kidney, which was alleviated by dapagliflozin treatment. Cell culture of immortalized renal tubular cells and macrophages unraveled that dapagliflozin could directly effect on these cells in vitro as an anti-inflammatory agent independent of glucose concentrations. We further proved that dapagliflozin attenuated ischemia/reperfusion-induced chronic kidney injury and renal inflammation in mice. Discussion: Overall, our data emphasize the importance of inflammatory factors to the pathogenesis of DKD, and provide valuable mechanistic insights into the renoprotective role of dapagliflozin.

Atypical form of Goodpasture's disease.

Goodpasture's disease and anti-glomerular basement membrane nephritis (anti-GBM nephritis) are rare autoimmune small vessel vasculitis predominantly affecting young men. Goodpasture's disease plays an important part in differential diagnosis of pulmonary - renal syndrome. The evidence of circulating autoantibodies, a typical histological appearance of the kidney biopsy with finding of the crescent glomerulonephritis and clinical presentation of nephritic syndrome play an important role in diagnosis. Our case report describes a case of a young male with anti-GBM nephritis that presents as rapidly progressive glomerulonephritis (RPGN) with progression to dialysis-dependent renal failure. The atypical sign of the case was development of nephrotic syndrome with volume-dependent hypertension. The case was complicated by heparin-induced thrombocytopenia. During combined immunosuppressive therapy with plasmapheresis, the condition of the patient has stabilized. However, renal function did not recover. This previously fatal disease has nowadays a very good survival rate because of immunosuppresion therapy, plasmapheresis and hemodialysis.

Secondary immunoglobulin A nephropathy with gross hematuria leading to rapidly progressive glomerulonephritis following severe acute respiratory syndrome coronavirus 2 vaccination: a case report.

BACKGROUND: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been followed by many reports of the development and relapse of autoimmune diseases associated with SARS-CoV-2 vaccination. Some of these reports have involved relapse or onset of immunoglobulin A (IgA) nephropathy following SARS-CoV-2 vaccination. Here, we report on a patient with IgA nephropathy who presented with gross hematuria and rapidly progressive glomerulonephritis following SARS-CoV-2 vaccination. CASE PRESENTATION: A 63-year-old male patient with a history of habitual tonsillitis underwent bilateral tonsillectomy. He had a history of alcoholic cirrhosis of the liver and microscopic hematuria and proteinuria were indicated during a health checkup 2 years before hospital admission. He developed hematuria after the SARS-CoV-2 vaccination, which led to rapidly progressive glomerulonephritis, for which he was hospitalized. A renal biopsy led to the diagnosis of IgA nephropathy. Although pulse steroid therapy during his condition resulted in hepatic encephalopathy, three courses combined with mizoribine improved his renal function. CONCLUSION: SARS-CoV-2 mRNA vaccines activate T cells, which are involved in the pathophysiology of IgA nephropathy. Therefore, this case suggests that the exacerbation of IgA nephropathy by the vaccine favors the vasculitis aspect of the disease.

Association of Interleukin-2 Gene Polymorphism with Henoch-schönlein Purpura Nephritis.

Henoch-Schönlein purpura nephritis (HSPN) is a common vasculitis that mostly affects children, and previous studies have indicated that genetic factors may influence disease susceptibility. The aim of this study was to evaluate a possible association of three interleukin-2 (IL-2) gene polymorphisms (rs3136534, rs2069776, and rs2069762) with HSPN in the Chinese population. A total of 81 patients with HSPN and 200 healthy children were enrolled. The distribution of genotypes, allelic frequencies, and haplotype frequencies among the three IL-2 polymorphisms were analyzed using the Sequenom MassARRAY system by means of matrix-assisted laser desorption ionization-time of flight mass spectrometry method. Compared to the healthy controls, genotyping analysis demonstrated rs3136534 was associated with a decreased HSPN risk in the dominant inheritance model (G/T+T/T vs. G/G; OR, 0.54; 95% CI, 0.31-0.93). However, the frequency of the T allele and haplotypes of rs3136534 showed no statistical significance. For the frequency of genotype, allele, and haplotype of the rs2069776 and rs20697622 polymorphisms, no significant differences were observed between HSPN patients and controls. Our results suggest that the rs3136534 polymorphism of the IL-2 gene is associated with susceptibility to HSPN in Chinese children.

Value of the modified semiquantitative classification in predicting outcomes in children with Henoch-Schönlein purpura nephritis.

BACKGROUND: The modified semiquantitative classification (SQC) is a new pathological classification for Henoch-Schönlein purpura nephritis (HSPN), and its prognostic value with regard to the outcomes of HSPN is unclear. METHODS: We performed a retrospective review of 249 patients with biopsy-proven HSPN admitted to the Children's Hospital of Chongqing Medical University. In addition to the International Study of Kidney Disease in Children (ISKDC) classification, renal biopsy specimens were also reevaluated according to the SQC. RESULTS: During the follow-up period of 2.9 (1.0-6.9) years, 14 (5.6%) patients reached the poor outcome at the end of follow-up. The SQC activity and chronicity indexes were positively correlated with the clinical manifestations, conventional pathology grades, and 24-h urinary protein (24hUP). The difference in the areas under the curve between the total biopsy SQC scores and ISKDC classification was 0.12 (p = .001, 95% CI: 0.0485-0.192). In the receiver operating characteristic (ROC) curve analysis of 1-year, 3-year, and 5-year poor outcomes and total biopsy SQC scores, a total biopsy score ≥10 was associated with a higher risk of an adverse outcome. CONCLUSION: Our study suggests that the SQC indexes are clearly correlated with the clinical and pathological findings of HSPN. The SQC is more sensitive than ISKDC classification for the prediction of the long-term outcomes of HSPN in children.

Nephroangiosclerosis: an update / Nefroangioesclerosis: actualización

Nephroangiosclerosis or kidney disease that accompanies chronic essential arterial hypertension has been known for more than a hundred years. The definitive diagnosis is established by renal biopsy, which is reserved for doubtful cases or atypical presentation, being in most cases a presumptive clinical diagnosis. The objective of this review is to analyse the main controversies that currently exist related to nephroangiosclerosis: inaccuracy in epidemiological aspects (prevalence and incidence unknown), diagnostic difficulties and lack of correlation studies between clinical data and histopathology, progression factors in Caucasians. Currently, with advances in genetic studies in hypertension, not using or redefining the term hypertensive kidney disease for another condition such as nephropathy related to the present genetic alteration is being considered. (AU)

La nefroangioesclerosis o enfermedad renal que acompaña a la hipertensión arterial esencial crónica, es una entidad conocida desde hace más de 100 años. El diagnóstico definitivo se establece por biopsia renal, la cual se reserva para casos dudosos o presentación atípica, siendo en la mayoría de casos un diagnóstico clínico de presunción. El objetivo de esta revisión es analizar las principales controversias que existen actualmente relacionadas con la nefroangioesclerosis: inexactitud en aspectos epidemiológicos (prevalencia e incidencia real desconocida), dificultades diagnósticas y falta de estudios de correlación entre datos clínicos e histopatología, factores de progresión en raza caucásica. Actualmente con los avances en estudios genéticos en hipertensión se está planteando abandonar o redefinir el término de enfermedad renal hipertensiva por otro como nefropatía relacionada con la alteración genética presente. (AU)

Clinical features, treatment and outcome of pediatric patients with severe cutaneous manifestations in IgA vasculitis: Multicenter international study.

OBJECTIVE: IgA vasculitis (IgAV) (formerly Henoch-Schönlein Purpura, HSP) rarely causes severe skin lesions in children. The purpose of the research was to determine whether severe skin manifestations were associated with a more severe disease course. METHODS: Severe cutaneous manifestations were defined as presence of hemorrhagic vesicles, bullae, ulcerations and/or necroses. Data were collected retrospectively from 12 international tertiary university medical centers. RESULTS: A total of 64 patients with the most severe skin changes in IgAV/HSP and median (Q1, Q3) age of 8.08 (5.08, 11.92) years at the disease onset were compared with 596 IgAV/HSP patients without these manfiestations and median (Q1, Q3) age of 6.33 (4.50, 8.92) years. The patients with severe cutaneous manifestations were older in comparison to other patients with IgAV/HSP (p<0.001), they developed nephritis more frequently (40.6% vs. 20.6%, p = 0.001) with worse outcome of renal disease (p = 0.001). This group of patients also had higher frequencies of severe gastrointestinal complications like hematochezia, massive bleeding and/or intussusception (29.3% vs. 14.8%, p<0.001). d-dimer concentrations were significantly higher in these patients (4.60 mg/L vs. 2.72 mg/L, p = 0.003) and they had more frequent need for treatment with systemic glucocorticoids (84.4% vs. 37.2%, p<0.001) in comparison with the control group. Further multivariate analysis showed that severe cutaneous changes were associated with higher risk of developing nephritis [OR=3.1 (95%CI 1.04-9.21), p = 0.042] and severe gastrointestinal complications [OR=3.65 (95%CI 1.08-12.37), p = 0.038]. CONCLUSION: Patients with IgAV/HSP and severe skin manifestations had a more severe clinical course and more frequently required glucocorticoids compared to classic IgAV/HSP patients.

Increased Immunoglobulin Gamma-3 Chain C in the Serum, Saliva, and Urine of Patients with Systemic Lupus Erythematosus.

Immunoglobulin gamma-3 chain C (IGHG3) levels have been detected in the blood and tissue of patients with systemic lupus erythematosus (SLE). This study aims to assess its clinical value by measuring and comparing levels of IGHG3 in different body fluids in patients with SLE. The levels of IGHG3 in saliva, serum, and urine from 181 patients with SLE and 99 healthy controls were measured and analyzed. In patients with SLE and healthy controls, salivary IGHG3 levels were 3078.9 ± 2473.8 and 1413.6 ± 1075.3 ng/mL, serum IGHG3 levels were 478.1 ± 160.9 and 364.4 ± 97.9 µg/mL, and urine IGHG3 levels were 64.0 ± 74.5 and 27.1 ± 16.2 ng/mL, respectively (all p < 0.001). Salivary IGHG3 was correlated with ESR (correlation coefficient [r], 0.173; p = 0.024). Serum IGHG3 was correlated with leukocyte count (r, -0.219; p = 0.003), lymphocyte count (r, 0.22; p = 0.03), anti-dsDNA antibody positivity (r, 0.22; p = 0.003), and C3 levels (r, -0.23; p = 0.002). Urinary IGHG3 was correlated with hemoglobin level (r, -0.183; p = 0.021), ESR (r, 0.204; p = 0.01), anti-dsDNA antibody positivity (r, 0.262; p = 0.001), C3 levels (r, -0.202; p = 0.011), and SLE disease activity index (r, 0.332; p = 0.01). Urinary IGHG3 was higher in patients with nephritis than in those without (119.5 ± 110.0 vs. 49.8 ± 54.4 ng/mL; p < 0.01). IGHG3 was increased in the saliva, serum, and urine of patients with SLE. While salivary IGHG3 was not identified to be specific to SLE disease activity, serum IGHG3 showed correlations with clinical characteristics. Urinary IGHG3 levels were associated with disease activity and renal involvement in SLE.

Prevalence and clinical significance of lymphadenopathy and its histological subtypes in patients with systemic lupus erythematosus: a retrospective cohort study.

The objective of this study was to evaluate the prevalence and the clinical significance of lymphadenopathy and its histological subtypes in patients with systemic lupus erythematosus. We conducted a retrospective cohort study of patients with SLE diagnosed using the 1997 ACR criteria, who were followed at our institution between 2008 and 2022. Patients were grouped based on the presence of SLE-attributed LAD and its histological phenotype, then compared in terms of demographic, clinical and laboratory characteristics. Of the 255 patients, 33.7% had SLE-attributed, 0.8% lymphoma-related and 0.4% tuberculosis-related LAD. Univariate analysis identified significant associations between the presence of LAD and fever (p < 0.0001), weight loss (p = 0.009), pericarditis (p = 0.004), myocarditis (p = 0.003), myositis (p = 0.034), leukopenia (p = 0.004), lymphopenia (p = 0.003), membranous nephritis (p = 0.004), anti-RNP (p = 0.001), anti-Smith (p = < 0.0001), and SSB antibodies (p = 0.038), and hypocomplementemia (C3:p = 0.019; C4:p < 0.0001). Logistic regression confirmed the associations of LAD with fever (OR = 3.277, 95% C.I 1.657-6.481), pericarditis (OR = 4.146, 95% C.I:1.577-10.899), membranous nephritis (OR = 3.586, 95% C.I:1.305-9.854), and leukopenia (OR = 2.611, 95%C.I:1.319-5.166), but not with weight loss, myocarditis, or myositis. Biopsy in a subset of patients (33.7% of total) revealed reactive/proliferative (62.1%) or necrotizing (37.9%) histological patterns. When we compared the histologic patterns, necrotizing LAD was associated with fever (p = 0.052), sicca (p = 0.018), and malar rash (p = 0.005). Most patients received corticosteroids, hydroxychloroquine, and/or DMARDs with relatively quick clinical improvement. In conclusion, LAD is a common SLE manifestation, associated with constitutional symptoms, myo-/pericarditis, myositis, cytopenia, and membranous nephritis. Despite relatively high prevalence of LAD in SLE, a biopsy may still be needed to rule out lymphoma.

IgA-dominant infection-related glomerulonephritis with NAPlr-positive tubulointerstitial nephritis.

Infection-related glomerulonephritis (IRGN) is one of the most common causes of acute kidney injury (AKI). Positive glomerular staining of the nephritis-associated plasmin receptor (NAPlr) has been reported as a useful biomarker of IRGN. Although the infection can provoke acute tubulointerstitial nephritis (AIN), there are few reports of positive staining for NAPlr with AIN. We report a case of methicillin-sensitive Staphylococcus aureus (MSSA) infection-related nephritis complicated with AIN, which showed positive staining for tubulointerstitial NAPlr. The patient developed AKI and nephrotic syndrome during an intraperitoneal MSSA infection. A diagnosis of IRGN complicated by infection-related acute tubulointerstitial nephritis (IRAIN) was made based on glomerular endocapillary proliferation with tubulointerstitial infiltrating cells and tubular atrophy. Tubulointerstitial infiltrating cells were positive for NAPlr staining and plasmin activity. Treatment of the infection by antibiotics and drainage did not improve the AKI, but steroid administration improved that. NAPlr evaluation is a helpful tool for identifying causes of AIN during infection.

Goodpasture syndrome and anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease is a rare life-threatening small vessel vasculitis that typically affects the capillaries of kidneys and lungs, with most of patients developing rapidly progressive crescentic glomerulonephritis, and 40%-60% concomitant alveolar haemorrhage. It is caused by the deposition in alveolar and glomerular basement membrane of circulating autoantibodies directed against antigens intrinsic to the basement membrane. The exact mechanism that induces the formation of autoantibodies is unknown, but probably environmental factors, infections or direct damage to kidneys and lungs may trigger the autoimmune response in genetically susceptible individuals. Initial therapy includes corticosteroids and cyclophosphamide to prevent autoantibodies production, and plasmapheresis to remove the circulating autoantibodies. Good renal outcomes may be achieved by a prompt treatment initiation. However, when patients present with severe renal failure requiring dialysis or with a high proportion of glomerular crescents at biopsy, renal outcomes are bad. Relapses are rare and when renal involvement is present, the suspect of concomitant diseases, such as ANCA-associated vasculitis and membranous nephropathy, should be raised. Imlifidase is showing promising results, which if confirmed will cause a paradigm shift in the treatment of this disease.

Urine Cell Transcriptomes Implicate Specific Renal Inflammatory Pathways Associated With Difficult-to-Control Hypertension.

Background The renal mechanisms involved in the maintenance of human hypertension and resistance to treatment are not well understood. Animal studies suggest that chronic renal inflammation contributes to hypertension. We studied cells shed in first-morning urine samples from individuals who were hypertensive who exhibited difficult-to-control blood pressure (BP). We performed bulk RNA sequencing of these shed cells to develop transcriptome-wide associations with BP. We also analyzed nephron-specific genes and used an unbiased bioinformatic approach to find signaling pathways activated in difficult-to-control hypertension. Methods and Results Participants who completed the SPRINT (Systolic Blood Pressure Intervention Trial) at a single trial site were recruited, and cells shed in first-morning urine samples collected. A total of 47 participants were divided into 2 groups based on hypertension control. The BP-difficult group (n=29) had systolic BP>140 mm Hg, >120 mm Hg after intensive treatment for hypertension, or required more than the median number of antihypertensive drugs used in SPRINT. The easy-to-control BP group (n=18) comprised the remainder of the participants. A total of 60 differentially expressed genes were identified with a >2-fold change in the BP-difficult group. In BP-difficult participants, 2 of the most upregulated genes were associated with inflammation: Tumor Necrosis Factor Alpha Induced Protien 6 (fold change, 7.76; P=0.006) and Serpin Family B Member 9 (fold change, 5.10; P=0.007). Biological pathway analysis revealed an overrepresentation of inflammatory networks, including interferon signaling, granulocyte adhesion and diapedesis, and Janus Kinase family kinases in the BP-difficult group (P<0.001). Conclusions We conclude that transcriptomes from cells shed in first-morning urine identify a gene expression profile in difficult-to-control hypertension that associates with renal inflammation.

Society for Maternal-Fetal Medicine Consult Series #64: Systemic lupus erythematosus in pregnancy.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, inflammatory autoimmune disease characterized by relapses (commonly called "flares") and remission. Many organs may be involved, and although the manifestations are highly variable, the kidneys, joints, and skin are commonly affected. Immunologic abnormalities, including the production of antinuclear antibodies, are also characteristic of the disease. Maternal morbidity and mortality are substantially increased in patients with systemic lupus erythematosus, and an initial diagnosis of systemic lupus erythematosus during pregnancy is associated with increased morbidity. Common complications of systemic lupus erythematosus include nephritis, hematologic complications such as thrombocytopenia, and a variety of neurologic abnormalities. The purpose of this document is to examine potential pregnancy complications and to provide recommendations on treatment and management of systemic lupus erythematosus during pregnancy. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend low-dose aspirin beginning at 12 weeks of gestation until delivery in patients with systemic lupus erythematosus to decrease the occurrence of preeclampsia (GRADE 1B); (2) we recommend that all patients with systemic lupus erythematosus, other than those with quiescent disease, either continue or initiate hydroxychloroquine (HCQ) in pregnancy (GRADE 1B); (3) we suggest that for all other patients with quiescent disease activity who are not taking HCQ or other medications, it is reasonable to engage in shared decision-making regarding whether to initiate new therapy with this medication in consultation with the patient's rheumatologist (GRADE 2B); (4) we recommend that prolonged use (>48 hours) of nonsteroidal antiinflammatory drugs (NSAIDs) generally be avoided during pregnancy (GRADE 1A); (5) we recommend that COX-2 inhibitors and full-dose aspirin be avoided during pregnancy (GRADE 1B); (6) we recommend discontinuing methotrexate 1-3 months and mycophenolate mofetil/mycophenolic acid at least 6 weeks before attempting pregnancy (GRADE 1A); (7) we suggest the decision to initiate, continue, or discontinue biologics in pregnancy be made in collaboration with a rheumatologist and be individualized to the patient (GRADE 2C); (8) we suggest treatment with a combination of prophylactic unfractionated or low-molecular-weight heparin and low-dose aspirin for patients without a previous thrombotic event who meet obstetrical criteria for antiphospholipid syndrome (APS) (GRADE 2B); (9) we recommend therapeutic unfractionated or low-molecular-weight heparin for patients with a history of thrombosis and antiphospholipid (aPL) antibodies (GRADE 1B); (10) we suggest treatment with low-dose aspirin alone in patients with systemic lupus erythematosus and antiphospholipid antibodies without clinical events meeting criteria for antiphospholipid syndrome (GRADE 2C); (11) we recommend that steroids not be routinely used for the treatment of fetal heart block due to anti-Sjögren's-syndrome-related antigen A or B (anti-SSA/SSB) antibodies given their unproven benefit and the known risks for both the pregnant patient and fetus (GRADE 1C); (12) we recommend that serial fetal echocardiograms for assessment of the PR interval not be routinely performed in patients with anti-SSA/SSB antibodies outside of a clinical trial setting (GRADE 1B); (13) we recommend that patients with systemic lupus erythematosus undergo prepregnancy counseling with both maternal-fetal medicine and rheumatology specialists that includes a discussion regarding maternal and fetal risks (GRADE 1C); (14) we recommend that pregnancy be generally discouraged in patients with severe maternal risk, including patients with active nephritis; severe pulmonary, cardiac, renal, or neurologic disease; recent stroke; or pulmonary hypertension (GRADE 1C); (15) we recommend antenatal testing and serial growth scans in pregnant patients with systemic lupus erythematosus because of the increased risk of fetal growth restriction (FGR) and stillbirth (GRADE 1B); and (16) we recommend adherence to the Centers for Disease Control and Prevention medical eligibility criteria for contraceptive use in patients with systemic lupus erythematosus (GRADE 1B).