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Introduction: Prior cross-sectional studies suggest that health-related quality of life (HRQOL) worsens with more severe glomerular disease. This longitudinal analysis was conducted to assess changes in HRQOL with changing disease status. Methods: Cure Glomerulonephropathy (CureGN) is a cohort of patients with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA vasculitis, or IgA nephropathy. HRQOL was assessed at enrollment and follow-up visits 1 to 3 times annually for up to 5 years with the Patient-Reported Outcomes Measurement Information System (PROMIS). Global health, anxiety, and fatigue domains were measured in all; mobility was measured in children; and sleep-related impairment was measured in adults. Linear mixed effects models were used to evaluate HRQOL responsiveness to changes in disease status. Results: A total of 469 children and 1146 adults with PROMIS scores were included in the analysis. HRQOL improved over time in nearly all domains, though group-level changes were modest. Edema was most consistently associated with worse HRQOL across domains among children and adults. A greater number of symptoms also predicted worse HRQOL in all domains. Sex, age, obesity, and serum albumin were associated with some HRQOL domains. The estimated glomerular filtration rate (eGFR) was only associated with fatigue and adult physical health; proteinuria was not associated with any HRQOL domain in adjusted models. Conclusion: HRQOL measures were responsive to changes in disease activity, as indicated by edema. HRQOL over time was not predicted by laboratory-based markers of disease. Patient-reported edema and number of symptoms were the strongest predictors of HRQOL, highlighting the importance of the patient experience in glomerular disease. HRQOL outcomes inform understanding of the patient experience for children and adults with glomerular diseases.

Introduction Glomerular diseases are characterized by variable disease activity over many years. We aimed to analyze the relationship between clinical disease activity and duration of glomerular disease. Methods Disease activity in adults with chronic minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy (IgAN; first diagnostic biopsy >5 years before enrollment; Of Longstanding Disease [OLD] cohort, n = 256) followed at Columbia University Medical Center (CUMC), was compared with disease activity of an internal and external cohort of patients with first diagnostic biopsy, Graphical abstract

Paraneoplastic glomerular diseases are caused by proteins and other molecules that are produced by, or in response to tumors. The paraprotein-associated glomerular diseases are well-characterized paraneoplastic syndromes, because evidence can be provided for the site of production (clonal plasma or B cell), the tumor product (circulating monoclonal immunoglobulin in the blood or urine) and end-organ damage (kidney biopsy showing involvement by the monoclonal protein). Other paraneoplastic glomerular diseases exist, such as cancer-associated membranous nephropathy and some podocytopathies. In this chapter, we review the paraneoplastic glomerular diseases.

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.

Introduction The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.

There is scant literature describing the effect of glomerular disease on health-related quality of life (HRQOL). The Cure Glomerulonephropathy study (CureGN) is an international longitudinal cohort study of children and adults with four primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy). HRQOL is systematically assessed using items from the Patient-Reported Outcomes Measurement Informative System (PROMIS). We assessed the relationship between HRQOL and demographic and clinical variables in 478 children and 1115 adults at the time of enrollment into CureGN. Domains measured by PROMIS items included global assessments of health, mobility, anxiety, fatigue, and sleep impairment, as well as a derived composite measure incorporating all measured domains. Multivariable models were created that explained 7 to 32% of variance in HRQOL. Patient-reported edema consistently had the strongest and most robust association with each measured domain of HRQOL in multivariable analysis (adjusted β [95% CI] for composite PROMIS score in children, -5.2 [-7.1 to -3.4]; for composite PROMIS score in adults, -6.1 [-7.4 to -4.9]). Female sex, weight (particularly obesity), and estimated glomerular filtration rate were also associated with some, but not all, domains of HRQOL. Primary diagnosis, disease duration, and exposure to immunosuppression were not associated with HRQOL after adjustment. Sensitivity analyses and interaction testing demonstrated no significant association between disease duration or immunosuppression and any measured domain of HRQOL. Thus, patient-reported edema has a consistent negative association with HRQOL in patients with primary glomerular diseases, with substantially greater impact than other demographic and clinical variables.

Focal segmental glomerulosclerosis (FSGS) is the histologic end point of many disease processes that affect the kidney. Clinically, adults with FSGS present with proteinuria that may be accompanied by the nephrotic syndrome. Once identifiable (secondary) causes are excluded, the diagnosis of idiopathic FSGS, a challenging glomerular disease to understand and manage, is made. On the basis of mostly retrospective data, first-line treatment for idiopathic FSGS patients with nephrotic-range proteinuria is a prolonged course of corticosteroids. However, steroid resistance is common and portends an increased risk of long-term decline in kidney function and end-stage kidney disease in these patients compared with responders. Multiple other immunosuppression regimens have been used in steroid-resistant FSGS, some of which have been studied in randomized controlled trials. Here, we review the data on the treatment for idiopathic FSGS in adults.

Clinical outcomes in ANCA-associated vasculitis (AAV) and lupus nephritis have improved greatly with treatment regimens containing high-dose glucocorticoids and cyclophosphamide. However, with the use of these medications come significant adverse events, most notably infections, cytopenias, malignancies, and reproductive abnormalities. Multiple recent randomized controlled trials in AAV and lupus nephritis have compared cyclophosphamide-based regimens with agents such as rituximab, mycophenolate mofetil, and azathioprine, with the hope of providing better clinical outcomes with improved safety profiles. Although some of these newer regimens are now considered first-line treatments of these diseases, their adverse event profiles have been disappointingly similar to those of cyclophosphamide-based protocols. Physicians and patients should consider the adverse event profiles generated by these trials in the context of their extensive use in other patient populations, as well as available measures to prevent such events, when choosing the ideal regimen for an individual patient.

Background Approximately 50% of patients with fibrillary glomerulonephritis (GN) progress to end-stage renal disease (ESRD) within 2 years of diagnosis, and no standard therapy exists. The data on rituximab therapy for fibrillary GN are limited and have inconsistent outcomes. Here, we report the largest case series to date using rituximab for fibrillary GN. Methods Retrospective chart reviews were conducted on 12 patients with fibrillary GN who were treated with rituximab (1 g i.v. × 2 doses or 375 mg/m(2) × 4 doses) at the Center for Glomerular Diseases at Columbia University Medical Center. Non-progression of disease was defined as stable/improved serum creatinine (SCr) with a minimum of 1 year of follow-up. Results The median SCr was 2.1 (range 0.7-2.7) mg/dL, median estimated glomerular filtration rate (eGFR) 39 (range 21-98) mL/min/1.73 m(2) and median proteinuria 4497 (range 210-7542) mg/day at the time of rituximab initiation. Four patients had received immunosuppression before rituximab, and nine received immunosuppression after rituximab, with four receiving a second rituximab course. Four of 12 patients were non-progressors, 3 of 12 had progressive renal dysfunction without reaching ESRD, and 5 patients reached ESRD. The median follow-up for patients who did not reach ESRD was 38 (range 14-76) months after rituximab treatment. Non-progressors had lower SCr values, higher eGFRs and shorter median duration from diagnosis to treatment than progressors. No serious adverse events were noted. Conclusions Rituximab therapy was associated with non-progression of renal disease in 4 of 12 patients. At the time of treatment, these non-progressors had better renal function and shorter time from diagnosis to treatment than progressors.

Glomerular diseases historically have been challenging disorders to comprehend and treat for patients and physicians alike. Kidney biopsy is the gold standard of diagnosis, but the link between pathophysiology and the histologic representation of kidney injury has remained elusive in many of these diseases. As a result, treatment of glomerular disease usually involves therapies that are not specific to disease pathogenesis, such as blockade of the renin-angiotensin-aldosterone system and various immunosuppression regimens. Recent research has resulted in greater insight into some glomerular diseases, leading to the hope that new diagnostic tests and treatments targeting disease-specific mechanisms are on the horizon. We review recent progress on the understanding, diagnosis, and treatment of 4 glomerular diseases: immunoglobulin A nephropathy, focal segmental glomerulosclerosis, the C3 glomerulopathies, and idiopathic membranous nephropathy.

Summary Background and objectives Adrenocorticotropic hormone (ACTH) has shown efficacy as primary and secondary therapy for nephrotic syndrome due to membranous nephropathy. The data on using ACTH to treat idiopathic FSGS are limited. This report describes our experience using ACTH for nephrotic syndrome due to idiopathic FSGS in the United States. Design, setting, participants, & measurements Twenty-four patients with nephrotic syndrome from idiopathic FSGS were treated with ACTH gel at two academic medical centers between 2009 and 2012, either as part of investigator-initiated pilot studies (n=16) or by prescription for treatment-resistant FSGS (n=8). The primary outcome was remission of proteinuria. The median dose of ACTH was 80 units injected subcutaneously twice weekly. Treatment durations were not uniform. Results Twenty-two patients had received immunosuppression (mean, 2.2 medications) before ACTH therapy. Six patients had steroid-dependent and 15 had steroid-resistant FSGS. At the time of ACTH initiation, the medianserumcreatinine(interquartilerange)was2.0(1.1–2.7)mg/dl,estimatedGFRwas36(28–78)ml/minper 1.73 m 2 , and urine protein-to-creatinine ratio was 4595 (2200–8020) mg/g. At the end of ACTH therapy, 7 of 24 patients (29%) experienced remission (n=2 complete remissions, n=5 partial remissions). All remitters had steroid-resistant (n=5) or steroid-dependent (n=2) FSGS. Two responders relapsed during the follow-up period (mean 6 SD, 70631 weeks). Adverse events occurred in 21 of 24 patients, including one episode of new-onset diabetes that resolved after stopping ACTH and two episodes of AKI. Conclusions Response to ACTH treatment among steroid-resistant or steroid-dependent patients with FSGS is low, but ACTH gel may be a viable treatment option for some patients with resistant nephrotic syndrome due to idiopathic FSGS. Further research is necessary to determine which patients will respond to therapy. Clin J Am Soc Nephrol 8: 2072–2081, 2013. doi: 10.2215/CJN.02840313

PURPOSE OF REVIEW Lupus nephritis occurs in as many as half of patients presenting with systemic lupus erythematosus and is a major predictor of morbidity and mortality in this patient population. Prior to the last decade, the treatment of lupus nephritis was largely limited to corticosteroids, high-dose alkylating agents, and azathioprine, and this therapy was broadly prescribed regardless of patient demographics, clinical presentation, or prior toxicities. RECENT FINDINGS Over the last decade, new immunomodulatory agents have emerged as effective induction and maintenance therapies in lupus nephritis. With these options, physicians are able to individualize the treatment regimens in an attempt to maximize clinical benefit and minimize adverse events. Moreover, the influence of patient demographics on disease severity and response to treatment has come to the forefront. SUMMARY Here, we review the recent progress made in the therapy of lupus nephritis with a focus on the randomized controlled trials which have demonstrated the efficacy of these new treatment regimens.

Available treatments for severe (class III, IV, and V) lupus nephritis (LN) have expanded greatly over the last 40 years. In the 1970s and 1980s, cyclophosphamide (CYC), in combination with glucocorticoids, gained favor as induction and maintenance therapy for severe LN. However, the adverse event profile of CYC led to the search for other medications for severe LN. Beginning in the late 1990 s, mycophenolate mofetil (MMF) was introduced as induction and maintenance therapy for severe LN. This review discusses the clinical trial results, pharmacology, cost-effectiveness, and adverse effect profiles of CYC compared to MMF for induction and maintenance therapy for severe LN. The authors conclude that MMF should be considered first-line induction and maintenance treatment therapy for severe LN, although CYC may have a place under specific clinical and economic circumstances.

Many patients with hypertension have uncontrolled disease. The dental visit presents a unique opportunity to screen patients for undiagnosed and undertreated hypertension, which may lead to improved monitoring and treatment. Although there are no clinical studies, it is generally recommended that nonemergent procedures be avoided in patients with a blood pressure of greater than 180/110 mm Hg. Because of the high prevalence of disease and medication use for hypertension, dentists should be aware of the oral side effects of antihypertensive medications as well as the cardiovascular effects of medications commonly used during dental visits.

OBJECTIVE. The purpose of our study is to present a series of 14 patients with chronic diverticulitis on barium enema examinations and to correlate the radiographic findings with the clinical and pathologic findings in these patients.CONCLUSION. Chronic diverticulitis is a distinct pathologic entity characterized by the frequent development of chronic obstructive symptoms and abdominal pain rather than the classic clinical findings of acute sigmoid diverticulitis. Barium enema examinations usually reveal a relatively long segment of circumferential narrowing in the sigmoid colon with a spiculated contour and tapered margins, sometimes associated with retrograde obstruction. Our experience suggests that chronic diverticulitis can often be diagnosed on the basis of the characteristic clinical and radiographic findings in these patients.

Minimal change disease (MCD) is the etiology of the nephrotic syndrome in the majority of children and up to one-fourth of adults with this condition. The pathophysiology of MCD is poorly understood, but recent studies suggest the roles of regulatory T-cell dysfunction and specific podocyte proteins in its pathogenesis. Oral glucocorticoids are considered first-line therapy for adult MCD and lead to remission in over 80 % of cases. Most patients experience relapse, and some develop glucocorticoid dependence or resistance with further treatment. Here we review the pathophysiology, clinical presentation, and treatment of MCD in adults.

Minimal change disease (MCD) is the etiology of 10%-25% of cases of nephrotic syndrome in adults. The mainstay of treatment for adult MCD, oral glucocorticoids, is based on two randomized controlled trials and extensive observational data in adults, and this treatment leads to remission in over 80% of cases. Relapses are common, and some patients become steroid-resistant (SR), steroid-dependent (SD), or frequently relapsing (FR). The data guiding the treatment of these patients are limited. Here, we review MCD in adults with particular focus on the evidence for immunosuppressive therapy in these patients.

This article presents the method of analyzing a mach 2 flow of air through a scramjet and over a cavity using hydroxyl tagging velocimetry (HTV). This method is of particular use in supersonic engines, where, fuel is ignited by a flame protected from airflow by a cavity. Emphasis of the experiment discussed is placed on the image analysis portion of the HTV experiments. The current software used to analyze laser intersections, created by Michigan State University, is user-intensive and inefficient because of the large number of inputs needed to produce a result. The conceptual method behind this imaging software is explained along with the mathematical algorithms related to the spatial correlation technique. The spatial correlation technique offers a way to determine the distance that an object has moved from one photograph to another. This work focuses on improvements to the dynamic analysis of images to expand the applicability of current software tools. The failures and successes of each method are explained.