Lupus nephritis kidney biopsy characteristics and preterm birth.

Individuals with lupus nephritis (LN) are at high risk of adverse maternal and fetal outcomes in pregnancy. Outside of pregnancy, proliferative lesions on kidney biopsies are associated with disease progression, but these have not been consistently associated with increased risk in pregnancy. This retrospective, single-center study examines how histologic findings, the timing from kidney biopsy to pregnancy, and the clinical features in the first trimester are associated with preterm birth among individuals with LN. Among 35 deliveries in 31 women, the mean gestational age at delivery was 33.8 weeks. The presence of a urine protein-to-creatinine ratio >0.5 g/g in the first trimester was associated with preterm delivery (81% vs. 36%, p = 0.04). Preterm birth was more common in individuals with glomerular crescents on biopsy (89% in those with >20% crescents vs. 50% in those with <20%, p = 0.06). A pregnancy occurring within 2 years after a kidney biopsy was more likely to result in preterm birth than if the biopsy was performed more than 2 years prior to conception (82% vs. 23%, p = 0.01). The time from diagnostic biopsy may be a surrogate for disease activity, and a 2-year delay from biopsy might allow sufficient time to achieve disease remission. Overall, these data could aid family planning discussions and promote preconception disease optimization for patients and their providers.

Examining the role of patient-reported external factors and risk of relapse in anti-neutrophilic cytoplasmic autoantibody vasculitis.

The role of stressors, insect bites, and infections on disease relapse of ANCA vasculitis has yet to be entirely explored, with limited retrospective studies focused on disease onset from small participant cohorts. Our study analyzes longitudinal survey data from 2011-2022 to evaluate this perspective from a large ANCA vasculitis cohort. We collected surveys every three to six months to obtain information on self-reported psychological stressors and significant life events, insect bites, and infections throughout clinical disease. We defined cohorts as those who relapsed (Relapse Cohort) and controls as those who did not relapse (Remission Cohort) during the study period. Survey responses were retrospectively reviewed during a 15-month timeframe prior to relapse or during 15 months of remission and categorized by type of stress event, insect bite, and infections at every available 3-month interval. There were no significant differences in stress and insect bites between the relapse and remission cohorts. Patients who relapsed reported more frequent upper respiratory infections and other infections, such as those affecting the skin and eyes, but there were no significant differences in the incidence of pulmonary or urinary infections compared to the remission cohort. There was a significant difference in reported upper respiratory infections 9 to 15 months prior to the relapse date, indicating a remote history of infections as a potentially significant physical stressor that may contribute to disease relapse. More frequent patient-reported infections, specifically upper respiratory infections, may contribute to patient vulnerability to relapse. Counseling and close monitoring of patients after infectious symptoms could aid in earlier detection of disease flares. Future studies are essential to further understand the importance of distal risk factors and how they impact relapse.

Relevance of Combined Clinicopathologic Phenotype and Antineutrophil Cytoplasmic Autoantibody Serotype in the Diagnosis of Antineutrophil Cytoplasmic Autoantibody Vasculitis.

Introduction: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), 2 major clinicopathologic variants of antineutrophil cytoplasmic autoantibody (ANCA) vasculitides, are mostly associated with proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, respectively. Less is known regarding the uncommon forms of ANCA vasculitis, PR3-ANCA MPA and MPO-ANCA GPA. Methods: In this cohort study we detailed the clinical presentation and outcome of patients with PR3-ANCA MPA and MPO-ANCA GPA from the Glomerular Disease Collaborative Network (GDCN) inception cohort. Baseline clinical manifestations, relapses, end-stage kidney disease (ESKD), and survival were compared within MPA cases by PR3-ANCA (n = 116) versus MPO-ANCA (n = 173) and within GPA cases by PR3-ANCA (n = 108) versus MPO-ANCA (n = 43). Fisher's exact test and Wilcoxon two sample test were used for comparisons. Proportional hazards models were used to evaluate the development of relapses, ESKD, and death. Results: Patients with PR3-ANCA MPA were younger (53 years vs. 62 years, P = 0.0007) and had increased prevalence of joint involvement (56% vs. 40%, P = 0.0115) and ear, nose, and throat (ENT) involvement (44% vs. 26%, P = 0.002) than MPO-ANCA MPA. Relapses, ESKD, and survival were similar between both MPA subsets. Within the GPA group, patients with MPO-ANCA GPA were older (61 years vs. 46 years, P = 0.0007) and more likely female (56% vs. 35%, P = 0.027) than PR3-ANCA GPA patients. MPO-ANCA GPA was also characterized by less prevalent ENT manifestations (58% vs. 77%, P = 0.028) and neurologic manifestations (5% vs. 25%, P = 0.0029), and increased ESKD and mortality. Conclusions: PR3-ANCA MPA and MPO-ANCA GPA are clinicopathologically distinct subsets of ANCA vasculitis that differ from MPO-ANCA MPA and PR3-ANCA GPA. Although the impact of these differences on the clinical management and outcome warrants further evaluation, these results support the recommendation of including both the phenotypic diagnosis and ANCA serotype in the diagnosis of ANCA vasculitis.

Hemodialysis-Related Complement and Contact Pathway Activation and Cardiovascular Risk: A Narrative Review.

Individuals receiving long-term hemodialysis are at increased risk of developing cardiovascular disease (CVD). Traditional cardiovascular risk factors do not fully explain the high CVD risk in this population. During hemodialysis, blood interacts with the biomaterials of the hemodialysis circuit. This interaction can activate the complement system and the factor XII-driven contact system. FXII activation triggers both the intrinsic pathway of coagulation and the kallikrein-kinin pathway, resulting in thrombin and bradykinin production, respectively. The complement system plays a key role in the innate immune response, but also contributes to the pathogenesis of numerous disease states. Components of the complement pathway, including mannose binding lectin and C3, are associated with CVD risk in people with end-stage kidney disease (ESKD). Both the complement system and the factor XII-driven contact coagulation system mediate proinflammatory and procoagulant responses that could contribute to or accelerate CVD in hemodialysis recipents. This review summarizes what is already known about hemodialysis-mediated activation of the complement system and in particular the coagulation contact system, emphasizing the potential role these systems play in the identification of new biomarkers for CVD risk stratification and the development of potential therapeutic targets or innovative therapies that decrease CVD risk in ESKD patients.

Association of Lupus Nephritis Histopathologic Classification With Venous Thromboembolism-Modification by Age at Biopsy.

INTRODUCTION: Lupus nephritis (LN) is an independent risk factor for venous thromboembolism (VTE). The risk of VTE has not been analyzed by International Society of Nephrology/Renal Pathology Society or World Health Organization LN class. Study goals were to measure VTE incidence in an LN patient cohort, to evaluate associations between VTE and LN class, and to investigate factors modifying associations between VTE and LN class. METHODS: A retrospective analysis was performed using Glomerular Disease Collaborative Network data. Image-confirmed VTE was compared between patients with any LN class V lesion and patients with only LN class III or IV. Logistic regression was used to calculate odds ratios and 95% confidence intervals. Effect modification was assessed between main effect and covariates. RESULTS: Our cohort consisted of 534 LN patients, 310 (58%) with class III/IV and 224 (42%) with class V with or without class III/IV, including 106 with class V alone. The VTE incidence was 62 of 534 (11.6%). The odds of VTE were not significantly different between patients with class III/IV and class V in adjusted analyses (odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.45-1.48). An age interaction was observed (P = 0.009), with increased odds of VTE with class III/IV diagnosed at a younger age (2.75, 0.90-8.41 estimated at age 16 years) and decreased odds with class III/IV diagnosed at an older age (0.23, 0.07-0.72 estimated at age 46 years), compared to class V. CONCLUSIONS: The VTE incidence was similar among patients with LN classes III/IV and V, suggesting that VTE risk is not limited to class V-related nephrotic syndrome and that age may modulate LN class-specific VTE risk.

Improving data quality in observational research studies: Report of the Cure Glomerulonephropathy (CureGN) network.

BACKGROUND: High data quality is of crucial importance to the integrity of research projects. In the conduct of multi-center observational cohort studies with increasing types and quantities of data, maintaining data quality is challenging, with few published guidelines. METHODS: The Cure Glomerulonephropathy (CureGN) Network has established numerous quality control procedures to manage the 70 participating sites in the United States, Canada, and Europe. This effort is supported and guided by the activities of several committees, including Data Quality, Recruitment and Retention, and Central Review, that work in tandem with the Data Coordinating Center to monitor the study. We have implemented coordinator training and feedback channels, data queries of questionable or missing data, and developed performance metrics for recruitment, retention, visit completion, data entry, recording of patient-reported outcomes, collection, shipping and accessing of biological samples and pathology materials, and processing, cataloging and accessing genetic data and materials. RESULTS: We describe the development of data queries and site Report Cards, and their use in monitoring and encouraging excellence in site performance. We demonstrate improvements in data quality and completeness over 4 years after implementing these activities. We describe quality initiatives addressing specific challenges in collecting and cataloging whole slide images and other kidney pathology data, and novel methods of data quality assessment. CONCLUSIONS: This paper reports the CureGN experience in optimizing data quality and underscores the importance of general and study-specific data quality initiatives to maintain excellence in the research measures of a multi-center observational study.

ANCA autoantigen gene expression highlights neutrophil heterogeneity where expression in normal-density neutrophils correlates with ANCA-induced activation.

ANCA vasculitis is an autoimmune disease with increased expression of the autoantigen genes, myeloperoxidase (MPO) and proteinase 3 (PRTN3), but the origin and significance of expression is less distinct. To clarify this, we measured MPO and PRTN3 messenger RNA in monocytes, normal-density neutrophils, and in enriched leukocytes from peripheral blood mononuclear cells. Increased autoantigen gene expression was detected in normal-density neutrophils and enriched leukocytes from patients during active disease compared to healthy individuals, with the largest difference in enriched leukocytes. RNA-seq of enriched leukocytes comparing active-remission pairs identified a gene signature for low-density neutrophils. Cell sorting revealed low-density neutrophils contained mature and immature neutrophils depending on the presence or absence of CD10. Both populations contributed to autoantigen expression but the frequency of immature cells in low-density neutrophils did not correlate with low-density neutrophil MPO or PRTN3 expression. Low-density neutrophils were refractory to MPO-ANCA induced oxidative burst, suggesting an alternative role for low-density neutrophils in ANCA vasculitis pathogenesis. In contrast, normal-density neutrophils were activated by MPO-ANCA and monoclonal anti-PR3 antibody. Normal-density neutrophil activation correlated with MPO and PRTN3 mRNA. Increased autoantigen gene expression originating from the mature low-density and normal-density neutrophils suggests transcriptional dysregulation is a hallmark of ANCA vasculitis. Thus, the correlation between autoantigen gene expression and antibody-mediated normal-density neutrophil activation connects autoantigen gene expression with disease pathogenesis.

Serum Albumin at Partial Remission Predicts Outcomes in Membranous Nephropathy.

BACKGROUND: In primary membranous nephropathy (MN), partial remission (PR) (≥50% reduction of proteinuria to <3.5 g/d) is associated with a greater risk of relapse and end-stage kidney disease (ESKD) compared with complete remission (CR). We aimed to determine factors associated with relapse or renal failure in patients who attain the standard definition of PR. METHODS: We captured PR, CR, relapse, and the composite of doubling of serum creatinine or ESKD in a cohort of 267 patients with MN, nephrotic syndrome, and >12 months of follow-up. Characteristics at the time of PR associated with the composite outcome or relapse were evaluated using a time-to-event analysis. RESULTS: A total of 192 patients attained PR and 86 attained CR. Serum albumin at PR (hazard ratio [HR]: 1.58 per 0.5 g/dl decrease from 4.0 g/dl; 95% confidence interval [CI]: 1.03-2.43) and duration of nephrotic proteinuria (HR: 1.01 per month increase; 95% CI: 1.00-1.03) were independent risk factors for the composite endpoint. Serum albumin at PR was associated with an increased risk of relapse (HR: 1.58 per 0.5 g/dl decrease below 4.0 g/dl; 95% CI: 1.24-2.01). A cutoff for serum albumin ≤3.5 g/dl at PR performed best in predicting relapse and composite outcome. CONCLUSIONS: Patients with serum albumin >3.5 g/dl at PR have decreased risk of composite outcome or relapse compared with PR with low albumin. A definition of PR that includes normalization of serum albumin may be a more robust surrogate endpoint in MN than the traditional definition of PR.

Measuring Circulating Complement Activation Products in Myeloperoxidase- and Proteinase 3-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVE: There is accumulating evidence that complement activation is important in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) pathogenesis. This study was undertaken to investigate complement activation in AAV with myeloperoxidase (MPO) positivity and AAV with proteinase 3 (PR3) positivity after determining optimal methods for measuring activated complement factors in circulation. METHODS: Participants included 98 patients with AAV (45 MPO-ANCA positive, 53 PR3-ANCA positive) and 35 healthy controls. Plasma was obtained from blood collected using EDTA tubes, with or without 100 µg/ml Futhan. Levels of Bb, C3a, C5a, soluble C5b-9 (sC5b-9), properdin, and C4d were measured by enzyme-linked immunosorbent assay. Group comparisons were made using Wilcoxon's 2-sample test. Paired data were analyzed using a matched pairs signed rank test. RESULTS: Compared to healthy controls, certain complement analyte levels were high in patients with active AAV with MPO positivity, including C3a (P < 0.0001), C5a (P = 0.0004), and sC5b-9 (P = 0.0007). During remission, levels of Bb (P = 0.001), C3a (P < 0.0001), and sC5b-9 (P = 0.003) were higher. Compared to healthy controls, C3a (P < 0.0001), C5a (P = 0.002), sC5b-9 (P = 0.0001), and C4d (P = 0.005) levels were higher in patients with active AAV with PR3 positivity; levels of C3a (P < 0.0001) and C4d (P = 0.007) were also higher duriing remission. There were no significant differences in any complement analyte for either ANCA serotype between patients with active disease and those with disease in remission. Among patients with paired samples, sC5-9 levels were significantly lower during disease remission compared to active disease. C5a was significantly lower among patients with disease in long-term remission who were not receiving therapy. For Bb, C5a, and sC5b-9, median levels and individual values were considerably higher in control and patient samples processed without Futhan compared to those processed with Futhan. CONCLUSION: Complement activation occurs in both MPO-positive AAV and PR3-positive AAV. The complement activation profile differs according to disease activity and possibly ANCA serotype. Futhan reduces in vitro complement activation and provides a more accurate measurement.

Understanding Long-term Remission Off Therapy in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

INTRODUCTION: In antineutrophil cytoplasmic antibody-associated (ANCA) vasculitis, relapse risk and long-term immunosuppressive therapy are problematic. Stopping immunotherapy has not been well described. METHODS: The Glomerular Disease Collaborative Network ANCA vasculitis inception cohort was evaluated. Patients who stopped all immunotherapy and those continuously on immunotherapy (≥2 years) were included. Time to first period off therapy was modeled with end-stage kidney disease and death as competing risks to understand influences of stopping therapy. Cause-specific hazard ratios (HRs) with 95% confidence intervals (CI) and P values are reported. Models controlled for age, sex, ANCA specificity, organ involvement, diagnosis era, and treatments (yes/no). Repeated events analysis was used to assess the time-dependent variable of time off treatment on recurrent relapse with HRs, 95% CIs, and P values are reported (same control variables without treatments). RESULTS: In 427 patients, 277 (65%) stopped therapy (median 20 months from initial induction); 14% for ≥2 different periods of time and 23% for periods ≥5 years. In multivariable models of time to discontinuation of treatment, women (HR 1.33; 95% CI 1.04-1.70; P = 0.024) and those treated with pulse methylprednisolone (HR 1.39; 95% CI 1.05-1.84; P = 0.020) were more likely to stop. The time-dependent variable of time off treatment was associated with fewer recurrent relapses (HR 0.51; 95% CI 0.41-0.63; P < 0.001). CONCLUSIONS: Stopping immunotherapy was common. Women and those treated with methylprednisolone stop treatment more often, but underlying mechanisms are unknown. Stopping treatment was associated with fewer relapses, suggesting that even without guidelines there may be benefits without an untoward detriment of relapse.

Immunoglobulins G from patients with ANCA-associated vasculitis are atypically glycosylated in both the Fc and Fab regions and the relation to disease activity.

BACKGROUND: Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against myeloperoxidase (MPO) and proteinase 3 (PR3) are pathogenic in ANCA-associated vasculitis (AAV). The respective role of IgG Fc and Fab glycosylation in mediating ANCA pathogenicity is incompletely understood. Herein we investigate in detail the changes in Fc and Fab glycosylation in MPO-ANCA and Pr3-ANCA and examine the association of glycosylation aberrancies with disease activity. METHODOLOGY: Total IgG was isolated from serum or plasma of a cohort of 30 patients with AAV (14 MPO-ANCA; 16 PR3-ANCA), and 19 healthy control subjects. Anti-MPO specific IgG was affinity-purified from plasma of an additional cohort of 18 MPO-ANCA patients undergoing plasmapheresis. We used lectin binding assays, liquid chromatography, and mass spectrometry-based methods to analyze Fc and Fab glycosylation, the degree of sialylation of Fc and Fab fragments and to determine the exact localization of N-glycans on Fc and Fab fragments. PRINCIPAL FINDINGS: IgG1 Fc glycosylation of total IgG was significantly reduced in patients with active AAV compared to controls. Clinical remission was associated with complete glycan normalization for PR3-ANCA patients but not for MPO-ANCA patients. Fc-glycosylation of anti-MPO specific IgG was similar to total IgG purified from plasma. A major fraction of anti-MPO specific IgG harbor extensive glycosylation within the variable domain on the Fab portion. CONCLUSIONS/SIGNIFICANCE: Significant differences exist between MPO and PR3-ANCA regarding the changes in amounts and types of glycans on Fc fragment and the association with disease activity. These differences may contribute to significant clinical difference in the disease course observed between the two diseases.

Intravenous pulse methylprednisolone for induction of remission in severe ANCA associated Vasculitis: a multi-center retrospective cohort study.

BACKGROUND: Intravenous pulse methylprednisolone (MP) is commonly included in the management of severe ANCA associated vasculitis (AAV) despite limited evidence of benefit. We aimed to evaluate outcomes in patients who had, or had not received MP, along with standard therapy for remission induction in severe AAV. METHODS: We retrospectively studied 114 consecutive patients from five centres in Europe and the United States with a new diagnosis of severe AAV (creatinine > 500 µmol/L or dialysis dependency) and that received standard therapy (plasma exchange, cyclophosphamide and high-dose oral corticosteroids) for remission induction with or without pulse MP between 2000 and 2013. We evaluated survival, renal recovery, relapses, and adverse events over the first 12 months. RESULTS: Fifty-two patients received pulse MP in addition to standard therapy compared to 62 patients that did not. There was no difference in survival, renal recovery or relapses. Treatment with MP associated with higher risk of infection during the first 3 months (hazard ratio (HR) 2.7, 95%CI [1.4-5.3], p = 0.004) and higher incidence of diabetes (HR 6.33 [1.94-20.63], p = 0.002), after adjustment for confounding factors. CONCLUSIONS: The results of this study suggest that addition of pulse intravenous MP to standard therapy for remission induction in severe AAV may not confer clinical benefit and may be associated with more episodes of infection and higher incidence of diabetes.

CureGN Study Rationale, Design, and Methods: Establishing a Large Prospective Observational Study of Glomerular Disease.

RATIONALE & OBJECTIVES: Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. EXPOSURES: Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. OUTCOMES: Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. ANALYTICAL APPROACH: The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years' initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0mL/min/1.73m2 in estimated glomerular filtration rate per year. LIMITATIONS: Current follow-up can only detect large differences in ESKD and death outcomes. CONCLUSIONS: Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.

Proteinase-3 and myeloperoxidase serotype in relation to demographic factors and geographic distribution in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

Background: In anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, antigen specificity varies between myeloperoxidase (MPO) and proteinase 3 (PR3). This has been reported to vary in relation to age, gender, geography and extrarenal manifestations. However, studies are difficult to compare as criteria for inclusion vary. The aim of this study was to investigate the relationship between ANCA serotype, latitude, ultraviolet (UV) radiation levels, age, gender and renal function at diagnosis in a large study with uniform inclusion criteria. Methods: Patients with biopsy-proven ANCA-associated glomerulonephritis were identified from regional or nationwide registries in 14 centres in Norway, Sweden, the UK, the Czech Republic, Croatia, Italy and the USA during the period 2000-13. UV radiation levels for 2000-13 in Europe were obtained from the Swedish Meteorological and Hydrological Institute. Results: A total of 1408 patients (45.2% PR3-ANCA) were included in the study. In univariable analysis, PR3-ANCA was significantly associated with male gender {odds ratio [OR] 2.12 [95% confidence interval (CI) 1.71-2.62]}, younger age [OR per year 0.97 (95% CI 0.96-0.98)] and higher glomerular filtration rate [OR per mL/min 1.01 (95% CI 1.01-1.02); P < 0.001] at diagnosis but not with latitude or UV radiation. In multivariable logistic regression analysis, latitude and UV radiation also became significant, with higher odds for PR3-ANCA positivity at northern latitudes/lower UV radiation levels. However, the latitudinal difference in MPO:PR3 ratio is smaller than differences previously reported concerning microscopic polyangiitis and granulomatosis with polyangiitis. Conclusions: The ratio between PR3-ANCA and MPO-ANCA varies in glomerulonephritis with respect to age, gender, renal function and geographic latitude/UV radiation levels.

Predicting Outcome in Patients with Anti-GBM Glomerulonephritis.

BACKGROUND AND OBJECTIVES: Large studies on long-term kidney outcome in patients with anti-glomerular basement membrane (anti-GBM) GN are lacking. This study aimed to identify clinical and histopathologic parameters that predict kidney outcome in these patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective analysis included a total of 123 patients with anti-GBM GN between 1986 and 2015 from six centers worldwide. Their kidney biopsy samples were classified according to the histopathologic classification for ANCA-associated GN. Clinical data such as details of treatment were retrieved from clinical records. The primary outcome parameter was the occurrence of ESRD. Kidney survival was analyzed using the log-rank test and Cox regression analyses. RESULTS: The 5-year kidney survival rate was 34%, with an improved rate observed among patients diagnosed after 2007 (P=0.01). In patients with anti-GBM GN, histopathologic class and kidney survival were associated (P<0.001). Only one of 15 patients with a focal class biopsy sample (≥50% normal glomeruli) developed ESRD. Patients with a sclerotic class biopsy sample (≥50% globally sclerotic glomeruli) and patients with 100% cellular crescents did not recover from dialysis dependency at presentation. In multivariable analysis, dialysis dependency at presentation (hazard ratio [HR], 3.17; 95% confidence interval [95% CI], 1.59 to 6.32), percentage of normal glomeruli (HR, 0.97; 95% CI, 0.95 to 0.99), and extent of interstitial infiltrate (HR, 2.02; 95% CI, 1.17 to 3.50) were predictors of ESRD during follow-up. CONCLUSIONS: Dialysis dependency, low percentage of normal glomeruli, and large extent of interstitial infiltrate are associated with poor kidney outcome in anti-GBM GN. Kidney outcome has improved during recent years; the success rate doubled after 2007. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_21_CJASNPodcast_18_1_v.mp3.

Provider perspectives on treatment decision-making in nephrotic syndrome.

BACKGROUND: Managing patients with nephrotic syndrome (NS) remains difficult for the practicing nephrologist. This often young patient population is faced with a debilitating, relapsing and remitting disease with non-specific treatment options that are often poorly tolerated. Clinicians managing these complex patients must attempt to apply disease-specific evidence while considering the individual patient's clinical and personal situation. METHODS: We conducted qualitative interviews to ascertain the provider perspectives of NS, treatment options and factors that influence recommendations for disease management, and administered a survey to assess both facilitators and barriers to the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. RESULTS: When making treatment recommendations, providers considered characteristics of various treatments such as efficacy, side effects and evaluation of risk versus benefit, taking into account how the specific treatment fit with the individual patient. Time constraints and the complexity of explaining the intricacies of NS were noted as significant barriers to care. Although the availability of guidelines was deemed a facilitator to care, the value of the KDIGO guidelines was limited by the perception of poor quality of evidence. CONCLUSIONS: The complexity of NS and the scarcity of robust evidence to support treatment recommendations are common challenges reported by nephrologists. Future development and use of shared learning platforms may support the integration of best available evidence, patient/family preferences and exchange of information at a pace that is unconstrained by the outpatient clinic schedule.