Search

Panduranga S Rao,1 Julie A Wright Nunes,1 Brenda W Gillespie,2 Rachel L Perlman,1 Rajan Ravichandran3 1Division of Nephrology, Department of Internal Medicine, University of Michigan Health System, 2Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA; 3Department of Nephrology, Madras Institute of Nephrology, Madras Institute of Orthopedics and Trauma Hospitals, Chennai, India Background: There is a paucity of information on kidney education and screening programs in Indian youth.Methods: Participants (n=2,158) from Chennai colleges were educated about the kidneys and chronic kidney disease (CKD) and screened in a pilot program from April to May 2013. This entailed: 1) a presentation and educational video and 2) an on-site assessment of weight, blood pressure, and demographic information. Urinalysis (UA) kits were distributed and returned in ≤48 hours. We examined participant characteristics and their association with dipstick proteinuria using logistic regression.Results: The mean (standard deviation [SD]) age was 18.9 (1.6) years, and 1,451 (68%) were men. Mean (SD) body mass index (BMI) was 21.9 (4.3) kg/m2; 745 (36%) had a BMI consistent with being overweight or obese. Mean (SD) systolic blood pressure (SBP) was 118.7 (13.1) mm Hg, and 94 (5%) of the participants had SBP ≥140. Mean (SD) diastolic blood pressure (DBP) was 70.9 (11.4) mm Hg, with 119 participants (6%) having ≥90 mm Hg. A total of 136 participants had glycosuria (UA≥1+) and 120 (6%) had proteinuria (UA≥1+). In unadjusted analyses, sex (odds ratio [OR]=1.64 [confidence interval, CI 1.06–2.55]; p=0.026 men vs. women) and age (OR=1.13 per year [CI 1.01–1.26]; p=0.032) were significantly associated with proteinuria. In the analysis adjusted for age, sex, SBP, DBP, glycosuria, and BMI, age remained independently associated with higher odds for proteinuria (OR=1.14 per year [1.02–1.29]; p=0.026). Males showed a trend of higher risk compared with women (OR=1.57 [CI 1.00–2.50]; p=0.051).Conclusion: This education and screening pilot program in a population of college students offers unique opportunities for identification, education, and early intervention for CKD. Keywords: screening, youth, CKD, proteinuria, glycosuria, education, hypertension, BMI, Indian youth

Background:Persistent pathogens have been proposed as risk factors for stroke; however, the evidence remains inconclusive. Mexican Americans have an increased risk of stroke especially at younger ages, as well as a higher prevalence of infections caused by

Objective: Lowering hemoglobin A(1c) to <7% reduces the risk of microvascular complications of diabetes, but the importance of maintaining this target in diabetes patients with kidney failure is unclear. We evaluated the relationship between A(1c) levels and mortality in an international prospective cohort study of hemodialysis patients.Research Design and Methods: Included were 9,201 hemodialysis patients from 12 countries (Dialysis Outcomes and Practice Patterns Study 3 and 4, 2006-2010) with type 1 or type 2 diabetes and at least one A(1c) measurement during the first 8 months after study entry. Associations between A(1c) and mortality were assessed with Cox regression, adjusting for potential confounders.Results: The association between A(1c) and mortality was U-shaped. Compared with an A(1c) of 7-7.9%, the hazard ratios (95% CI) for A(1c) levels were 1.35 (1.09-1.67) for <5%, 1.18 (1.01-1.37) for 5-5.9%, 1.21 (1.05-1.41) for 6-6.9%, 1.16 (0.94-1.43) for 8-8.9%, and 1.38 (1.11-1.71) for ≥9.0%, after adjustment for age, sex, race, BMI, serum albumin, years of dialysis, serum creatinine, 12 comorbid conditions, insulin use, hemoglobin, LDL cholesterol, country, and study phase. Diabetes medications were prescribed for 35% of patients with A(1c) <6% and not prescribed for 29% of those with A(1c) ≥9%.Conclusions: A(1c) levels strongly predicted mortality in hemodialysis patients with type 1 or type 2 diabetes. Mortality increased as A(1c) moved further from 7-7.9%; thus, target A(1c) in hemodialysis patients may encompass values higher than those recommended by current guidelines. Modifying glucose-lowering medicines for dialysis patients to target A(1c) levels within this range may be a modifiable practice to improve outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We compared 3 methods for classifying methicillin-resistant Staphylococcus aureus (MRSA) infections as health care associated or community associated for use in public health surveillance. METHODS: We analyzed data on MRSA infections reported to the Michigan Department of Community Health from October 1, 2004, to December 31, 2005. Patient demographics, risk factors, infection information, and susceptibility were collected for 2151 cases. We classified each case by the health care risk factor, infection-type, and susceptibility pattern methods and compared the results of the 3 methods. RESULTS: Demographic, clinical, and microbiological variables yielded similar health care-associated and community-associated distributions when classified by risk factor and infection type. When 2 methods yielded the same classifications, the overall distribution was similar to classification by 3 methods. No specific combination of 2 methods was superior. CONCLUSIONS: MRSA categorization by 2 methods is more accurate than it is by a single method. The health care risk factor and infection-type methods yield comparable classification results. Accuracy is increased by using more variables; however, further research is needed to identify the optimal combination. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hemodialysis patients are at increased risk of amputation, particularly those with diabetes. Limited data exist about the prevalence, incidence, risk factors for, and sequelae of amputation in hemodialysis patients. STUDY DESIGN: A prospective observational study of hemodialysis practices and outcomes. SETTING & PARTICIPANTS: Data from 29,838 patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) from 1996 to 2004 were analyzed. PREDICTOR/FACTOR: Demographic factors, comorbid conditions, laboratory values, years since end-stage renal disease onset, and currently prescribed medications at study enrollment. OUTCOME: Prior amputation at study enrollment by using logistic regression and amputation during follow-up by using Cox models. Amputation was ascertained from medical record review. RESULTS: There was a high prevalence (6%) and incidence (2.0 events/100 patient-years at risk) of amputation in hemodialysis patients; patients with diabetes had a more than 9 times greater incidence of new amputation. Wide variations among countries were observed in risk of amputation, with the lowest prevalence in Japan and the highest in Belgium, France, and Germany. Traditional cardiovascular risk factors, such as age, peripheral vascular disease, and smoking were predictive of amputation, as were such risk factors related to hemodialysis as altered mineral metabolism and years of hemodialysis therapy. In patients with diabetes, greater relative risks of amputation were observed in men, smokers, and those with other diabetic complications, anemia, and malnutrition. The relative risk of mortality after amputation was 1.54 (95% confidence interval, 1.41 to 1.68; P < 0.001) with a mean survival of 2.0 versus 3.8 years. LIMITATIONS: The database does not differentiate between types of amputations; some amputations may have concerned the upper limbs and could have been linked to ischemia related to vascular access. CONCLUSIONS: Amputation in hemodialysis patients is a very frequent event, particularly in patients with diabetes, and is associated with both traditional cardiovascular risk factors and factors linked to kidney failure treated by hemodialysis. Interventional trials are needed to reduce the burden of amputation. Copyright © 2009 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Digital chest imaging has replaced film chest radiographs in many centers, but the International Labour Organization classification system, which is the most widely used system for recognition and classification of dust-related abnormalities, is predicated on film chest radiographs. The purpose of this study was to evaluate the equivalency of digital chest radiographs (including both hard copy and soft copy) with film radiographs for the recognition and quantification of abnormalities consistent with pneumoconiosis using the International Labour Organization classification system. Materials and Methods: Digital chest images and film images, obtained from 107 subjects with a range of parenchymal and pleural abnormalities, were classified in random order by six B readers. Results: Readings of film and soft copy images were equivalent for small opacity profusion; readings of hard copy images had significantly greater prevalence of small opacities compared to film and soft copy. The prevalence of large opacities differed significantly among all three image formats: hard copy greater than film greater than soft copy. However, film and soft copy readings for large opacities did not differ significantly when images demonstrating the coalescence of small opacities that had not yet become a large opacity were grouped with large opacities. The prevalence of pleural abnormalities differed significantly among all three image formats: film greater than hard copy greater than soft copy. Conclusions: Film and soft copy images can be recommended for the recognition and classification of dust-related parenchymal abnormalities using International Labour Organization classifications. The role of digital radiography in reading for pleural abnormalities requires additional investigation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Abnormalities in serum calcium, phosphorus, and parathyroid hormone (PTH) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality. No clinical trials have been conducted to clearly identify categories of calcium, phosphorus, and PTH levels associated with the lowest mortality risk. Current clinical practice guidelines are based largely on expert opinions, and clinically relevant differences exist among guidelines across countries. We sought to describe international trends in calcium, phosphorus, and PTH levels during 10 years and identify mortality risk categories in the Dialysis Outcomes and Practice Patterns Study (DOPPS), an international study of hemodialysis practices and associated outcomes. STUDY DESIGN: Prospective cohort study. PARTICIPANTS: 25,588 patients with end-stage renal disease on hemodialysis therapy for longer than 180 days at 925 facilities in DOPPS I (1996-2001), DOPPS II (2002-2004), or DOPPS III (2005-2007). PREDICTORS: Serum calcium, albumin-corrected calcium (Ca(Alb)), phosphorus, and PTH levels. OUTCOMES: Adjusted hazard ratios for all-cause and cardiovascular mortality calculated using Cox models. RESULTS: Distributions of mineral metabolism markers differed across DOPPS countries and phases, with lower calcium and phosphorus levels observed in the most recent phase of DOPPS. Survival models identified categories with the lowest mortality risk for calcium (8.6 to 10.0 mg/dL), Ca(Alb) (7.6 to 9.5 mg/dL), phosphorus (3.6 to 5.0 mg/dL), and PTH (101 to 300 pg/mL). The greatest risk of mortality was found for calcium or Ca(Alb) levels greater than 10.0 mg/dL, phosphorus levels greater than 7.0 mg/dL, and PTH levels greater than 600 pg/mL and in patients with combinations of high-risk categories of calcium, phosphorus, and PTH. LIMITATIONS: Because of the observational nature of DOPPS, this study can only indicate an association between mineral metabolism categories and mortality. CONCLUSIONS: Our results provide important information about mineral metabolism trends in hemodialysis patients in 12 countries during a decade. The risk categories identified in the DOPPS cohort may be relevant to efforts at international harmonization of existing clinical guidelines for mineral metabolism. [ABSTRACT FROM AUTHOR]

BACKGROUND: We investigated aspirin-prescribing patterns and potential benefits on cardiovascular morbidity and mortality in hemodialysis patients. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: Data included 28,320 randomly selected hemodialysis patients from the Dialysis Outcomes and Practice Patterns Study I and II. PREDICTOR: Aspirin prescription at study baseline. OUTCOMES & MEASUREMENTS: Prescription was investigated by means of logistic regression. All-cause mortality, all-cause hospitalization, cardiac event, myocardial infarction, cerebrovascular (CVA), gastrointestinal bleed, transient ischemic attack, and subdural hematoma were examined. Cox regression examined the risk of mortality and hospitalization. All models accounted for facility clustering and demographics and comorbid conditions. RESULTS: Wide variation was found in aspirin prescription, from 8% in Japan to 41% in Australia and New Zealand. Characteristics significantly associated with increased odds of prescription included coronary artery disease, cerebrovascular disease, diabetes, male sex, nonblack race, peripheral vascular disease, age, hypertension, and absence of gastrointestinal bleeding. Aspirin was associated with decreased risk of stroke in all patients (relative risk [RR], 0.82; P < 0.01) and increased risk of myocardial infarction (RR, 1.21; P = 0.01) and cardiac event (RR, 1.08; P < 0.01) in all patients, with similar results for patients with coronary artery disease. There was no increase in gastrointestinal bleeding. LIMITATIONS: Observational studies are not protected from biases, despite adjustments. There is potential for aspirin use to be underreported because of its availability without prescription. CONCLUSIONS: The hypothesis that prescribing aspirin to hemodialysis patients decreases cardiovascular disease risk is not supported. Aspirin might decrease CVA and appears not to increase hemorrhagic risk. This should be an incentive for randomized controlled trials. Copyright © 2007 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND: Information about residual renal function (RRF) and outcomes associated with practices of diuretic use in patients with end-stage renal disease is not available worldwide. METHODS: Diuretic use was investigated in 16,420 hemodialysis patients from the Dialysis Outcomes and Practice Patterns Study, a prospective observational study of hemodialysis patients selected from nationally representative facilities on 3 continents. Logistic regressions were used to investigate associations between diuretic use and patient characteristics. Outcomes of interdialytic weight gain, increased serum potassium and phosphorus levels, and odds of retaining RRF after 1 year were investigated. Cox regression was used to analyze the association between mortality and diuretic use. RESULTS: Facility diuretic use varied substantially from 0% to 83.9% of patients. Diuretic use decreased sharply after the start of dialysis therapy. Loop diuretic use ranged from 9.2% in the United States to 21.3% in Europe, whereas use within 90 days of starting dialysis therapy ranged from 25.0% in the United States to 47.6% in Japan. Diuretic use was associated with lower interdialytic weight gain and lower odds of hyperkalemia (potassium > 6.0 mmol/L). Patients with RRF on diuretic therapy had almost twice the odds of retaining RRF after 1 year in the study versus patients not on diuretic therapy. Patients administered diuretics had a 7% lower all-cause mortality risk (P = 0.12) and 14% lower cardiac-specific mortality risk (P = 0.03) versus patients not administered diuretics. CONCLUSION: Variation exists in facility practices of diuretic use. In patients with RRF, there may be benefit associated with continuing diuretic use rather than automatically discontinuing diuretic therapy at dialysis initiation. Copyright © 2007 by the National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

There are numerous causes for slow or delayed wound healing. Because slowly healing wounds are often inflamed, we quantitated the inflammatory chemokine, interleukin-8, produced by slowly healing human burn wounds and compared this to interleukin-8 from healed wounds and normal intact skin. Interleukin-8 levels were increased significantly in unhealed wounds (19.7 ng/ml) compared to healed wounds (7.7 ng/ml) or normal skin (5.7 ng/ml). Interleukin-8 in these ranges was added to adult human keratinocytes and fibroblasts. Interleukin-8 significantly decreased keratinocyte replication but had no effect on fibroblast replication. The rate or final degree of fibroblast populated collagen lattice contraction was inhibited at interleukin-8 concentrations between 10 and 30 ng/ml, but not altered at concentrations below 10 ng/ml and above 100 ng/ml. The concurrent application of indomethacin at 10 mg/ml reversed this interleukin-8 induced inhibition. Interleukin-8 inhibited myosin ATPase activity, apparently by reducing the phosphorylation of nonmuscle myosin light chain. We conclude that elevated levels of interleukin-8 may be found during delayed healing, and these elevated interleukin-8 levels may directly contribute to retarded wound closure. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis affects approximately 20% of women annually, but it is not well characterized epidemiologically. Of 1027 respondents to two mailed cross-sectional surveys at a large university, 37.5% reported a prior clinical diagnosis of vulvovaginal candidiasis. The frequency of first diagnosis increased rapidly after age 17, with an estimated 54.7% of women experiencing the condition by age 25. In a proportional hazards model of age at first diagnosis, vulvovaginal candidiasis was associated with initiation of sexual activity (rate ratio [RR] = 2.9; 95% confidence interval [CI] = 2.2, 3.8), oral contraceptive use (RR = 1.7; CI = 1.4, 2.2), and White (RR = 3.1; CI = 1.7, 5.7) and Black (RR = 5.9; CI = 3.0, 11.5) race vs Asian. [ABSTRACT FROM AUTHOR]

BACKGROUNDIt is unknown whether the risk of kidney disease progression and failure differs between patients with and without genetic kidney disorders.METHODSThree cohorts were evaluated: the prospective Cure Glomerulonephropathy Network (CureGN) and 2 retrospective cohorts from Columbia University, including 5,727 adults and children with kidney disease from any etiology who underwent whole-genome or exome sequencing. The effects of monogenic kidney disorders and APOL1 kidney-risk genotypes on the risk of kidney failure, estimated glomerular filtration rate (eGFR) decline, and disease remission rates were evaluated along with diagnostic yields and the impact of American College of Medical Genetics secondary findings (ACMG SFs).RESULTSMonogenic kidney disorders were identified in 371 patients (6.5%), high-risk APOL1 genotypes in 318 (5.5%), and ACMG SFs in 100 (5.2%). Family history of kidney disease was the strongest predictor of monogenic disorders. After adjustment for traditional risk factors, monogenic kidney disorders were associated with an increased risk of kidney failure (hazard ratio [HR] = 1.72), higher rate of eGFR decline (-3.06 vs. 0.25 mL/min/1.73 m2/year), and lower risk of complete remission (odds ratioNot achieving CR = 5.25). High-risk APOL1 genotypes were associated with an increased risk of kidney failure (HR = 1.67) and faster eGFR decline (-2.28 vs. 0.25 mL/min/1.73 m2), replicating prior findings. ACMG SFs were not associated with personal or family history of associated diseases, but were predicted to impact care in 70% of cases.CONCLUSIONSMonogenic kidney disorders were associated with an increased risk of kidney failure, faster eGFR decline, and lower rates of complete remission, suggesting opportunities for early identification and intervention based on molecular diagnosis.TRIAL REGISTRATIONNA.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases grants U24DK100845 (formerly UM1DK100845), U01DK100846 (formerly UM1DK100846), U01DK100876 (formerly UM1DK100876), U01DK100866 (formerly UM1DK100866), U01DK100867 (formerly UM1DK100867), U24DK100845, DK081943, RC2DK116690, 2U01DK100876, 1R01DK136765, 5R01DK082753, and RC2-DK122397; NephCure Kidney International; Department of Defense Research Awards PR201425, W81XWH-16-1-0451, and W81XWH-22-1-0966; National Center for Advancing Translational Sciences grant UL1TR001873; National Library of Medicine grant R01LM013061; National Human Genome Research Institute grant 2U01HG008680.

Rationale & Objective: Adolescent- and adult-onset minimal change disease (MCD) may have a clinical course distinct from childhood-onset disease. We characterized the course of children and adults with MCD in the Cure Glomerulonephropathy Network (CureGN) and assessed predictors of rituximab response., Study Design: Prospective, multicenter, observational study., Study Participants: CureGN participants with proven MCD on biopsy., Exposure: Age at disease onset, initiation of renin-angiotensin-aldosterone system (RAAS) blockade, and immunosuppression including rituximab during the study period., Outcome: Relapse and remission, change in estimated glomerular filtration rate (eGFR), and kidney failure., Analytical Approach: Remission and relapse probabilities were estimated using Kaplan-Meier curves and gap time recurrent event models. Linear regression models were used for the outcome of change in eGFR. Cox proportional hazards models were used to estimate the association between rituximab administration and remission., Results: The study included 304 childhood- (≤12 years old), 49 adolescent- (13-17 years old), and 201 adult- (≥18 years) onset participants with 2.7-3.2 years of follow-up after enrollment. Children had a longer time to biopsy (238 vs 23 and 36 days in adolescent- and adult-onset participants, respectively; P<0.001) and were more likely to have received therapy before biopsy. Children were more likely to be treated with immunosuppression but not RAAS blockade. The rate of relapse was higher in childhood- versus adult-onset participants (HR, 1.69 [95% CI, 1.29-2.21]). The probability of remission was also higher in childhood-onset disease (HR, 1.33 [95%CI, 1.02-1.72]). In all groups eGFR loss was minimal. Children were more likely to remit after rituximab than those with adolescent- or adult-onset disease (adjusted HR, 2.1; P=0.003). Across all groups, glucocorticoid sensitivity was associated with a greater likelihood of achieving complete remission after rituximab (adjusted HR, 2.62; P=0.002)., Limitations: CureGN was limited to biopsy-proven disease. Comparisons of childhood to nonchildhood cases of MCD may be subject to selection bias, given that childhood cases who undergo a biopsy may be limited to patients who are least responsive to initial therapy., Conclusions: Among patients with MCD who underwent kidney biopsy, there were differences in the course (relapse and remission) of childhood-onset compared with adolescent- and adult-onset disease, as well as rituximab response., Plain-Language Summary: Minimal change disease is a biopsy diagnosis for nephrotic syndrome. It is diagnosed in childhood, adolescence, or adulthood. Patients and clinicians often have questions about what to expect in the disease course and how to plan therapies. We analyzed a group of patients followed longitudinally as part of the Cure Glomerulonephropathy Network (CureGN) and describe the differences in disease (relapse and remission) based on the age of onset. We also analyzed rituximab response. We found that those with childhood-onset disease had a higher rate of relapse but also have a higher probability of reaching remission when compared with adolescent- or adult-onset disease. Children and all steroid-responsive patients are more likely to achieve remission after rituximab., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Caffeine has long been vilified as a cause for urinary urgency incontinence (UUI) along with other potential bladder irritants such as carbonation, alcohol, and acidic juices. The objective of this study was to assess the fluid intake behavior of people with urgency, UUI, and those with lower urinary tract symptoms (LUTS) without UUI or urgency to assess if they avoided certain potential bladder irritants or had different fluid intake. We hypothesized that patients with UUI would avoid caffeine as a self-management method more so than these other two groups., Methods: Treatment-seeking men and women with LUTS in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort study completed a baseline 3-day voiding and intake diary. "Complete" diaries had 3 days of data and no missing intake or voided volumes. Beverages with any caffeine, alcohol, carbonation, or acidic juice were identified and the total volume was recorded as well as the type of beverage containing caffeine to calculate the daily caffeine dose., Results: Four hundred and ninety-one participants (277 men and 214 women) with a median age of 63 had complete diaries. Urinary urgency was more prevalent in women than men (79% vs. 55%, p < 0.0001) as was UUI (84% vs. 47%, p < 0.0001). Total fluid intake over 3 days was lower among the urgency group versus the nonurgency group (median [interquartile range] 5.2 [4.0-6.8] L vs. 5.7 [4.3-7.0] L, p = 0.028) and the UUI group compared to the urgency without incontinence group were less likely to consume alcohol (26% vs. 37%, p = 0.04). After adjusting for sex, BMI, age, and total intake volume, UUI participants had 54% lower odds of consuming any caffeine (odds ratio = 0.46, 95% confidence interval = 0.22-0.96, p = 0.04) than those without incontinence, but among those that did consume caffeine, no difference in the volume of caffeinated beverages or milligrams of caffeine consumed was detected between those with UUI and those with urgency without incontinence. No difference in carbonation or acidic juice intake was detected between groups., Conclusions: Individuals with urgency consume a lower volume of fluid than those without urgency. UUI participants more often abstain from caffeine, but among those that consume caffeine, the dose is similar to those without UUI. One explanation for these results is that only a subset of individuals with urgency or UUI are caffeine sensitive., (© 2022 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Background: Heterogeneity in disease course and treatment response among patients with MCD/FSGS necessitates a granular evaluation of kidney tissue features. This study aimed to identify histologic and ultrastructural descriptors of structural changes most predictive of clinical outcomes in the Nephrotic Syndrome Study Network (NEPTUNE)., Methods: Forty-eight histologic (37 glomerular, 9 tubulointerstitial, 2 vascular) and 20 ultrastructural descriptors were quantified by applying the NEPTUNE Digital Pathology Scoring System to NEPTUNE kidney biopsies. Outcomes included time from biopsy to disease progression, first complete remission of proteinuria, and treatment response. Relative importance of pathology and clinical predictors was obtained from random forest models, and predictive discrimination was assessed., Results: Among 224 participants (34% Black, 24% Hispanic), model performance was excellent, with predictive discrimination of 0.9 for disease progression, 0.85 for complete remission, and 0.81 for treatment response. The most predictive descriptors of outcomes included both conventional- e.g. , global sclerosis or segmental sclerosis and interstitial fibrosis/tubular atrophy-and novel features, including adhesion, interstitial foam cells, deflation, periglomerular fibrosis, mononuclear white blood cells, endothelial cell abnormalities, microvillous transformation, and acute tubular injury., Conclusions: The most predictive descriptors of clinical outcomes among MCD/FSGS patients reflected structural changes in multiple renal compartments. Reporting these descriptors should be standardized to guide prognostication of proteinuric glomerular diseases., (Copyright © 2022 by the American Society of Nephrology.)

We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data types (continuous and categorical) required novel methodology using a weighted Tanimoto indices approach. Data domains only available on a subset of the cohort were integrated using a semi-supervised clustering approach. Novel contrast criterion for determination of the optimal number of clusters in consensus clustering was introduced and compared with existing criteria. Distinctiveness of the clusters was confirmed by using multiple criteria for cluster quality, and by testing for significantly different variables in pairwise comparisons of the clusters. Cluster dynamics were explored by analyzing longitudinal data at 3- and 12-month follow-up. Five clusters of women with LUTS were identified using the developed methodology. None of the clusters could be characterized by a single symptom, but rather by a distinct combination of symptoms with various levels of severity. Targeted proteomics of serum samples demonstrated that differentially abundant proteins and affected pathways are different across the clusters. The clinical relevance of the identified clusters is discussed and compared with the current conventional approaches to the evaluation of LUTS patients. The rationale and thought process are described for the selection of procedures for data preprocessing, clustering, and cluster evaluation. Suggestions are provided for minimum reporting requirements in publications utilizing clustering methodology with multiple heterogeneous data domains., Competing Interests: The authors have declared that no competing interests exist.

Rationale & Objective: The current classification system for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) does not fully capture the complex structural changes in kidney biopsies nor the clinical and molecular heterogeneity of these diseases., Study Design: Prospective observational cohort study., Setting & Participants: 221 MCD and FSGS patients enrolled in the Nephrotic Syndrome Study Network (NEPTUNE)., Exposure: The NEPTUNE Digital Pathology Scoring System (NDPSS) was applied to generate scores for 37 glomerular descriptors., Outcome: Time from biopsy to complete proteinuria remission, time from biopsy to kidney disease progression (40% estimated glomerular filtration rate [eGFR] decline or kidney failure), and eGFR over time., Analytical Approach: Cluster analysis was used to group patients with similar morphologic characteristics. Glomerular descriptors and patient clusters were assessed for associations with outcomes using adjusted Cox models and linear mixed models. Messenger RNA from glomerular tissue was used to assess differentially expressed genes between clusters and identify genes associated with individual descriptors driving cluster membership., Results: Three clusters were identified: X (n = 56), Y (n = 68), and Z (n = 97). Clusters Y and Z had higher probabilities of proteinuria remission (HRs of 1.95 [95% CI, 0.99-3.85] and 3.29 [95% CI, 1.52-7.13], respectively), lower hazards of disease progression (HRs of 0.22 [95% CI, 0.08-0.57] and 0.11 [95% CI, 0.03-0.45], respectively), and lower loss of eGFR over time compared with X. Cluster X had 1,920 genes that were differentially expressed compared with Y+Z; these reflected activation of pathways of immune response and inflammation. Six descriptors driving the clusters individually correlated with clinical outcomes and gene expression., Limitations: Low prevalence of some descriptors and biopsy at a single time point., Conclusions: The NDPSS allows for categorization of FSGS/MCD patients into clinically and biologically relevant subgroups, and uncovers histologic parameters associated with clinical outcomes and molecular signatures not included in current classification systems., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Inflammation and oxidative stress contribute to the disproportionate burden of cardiovascular disease (CVD) in chronic kidney disease (CKD). Disordered catabolism of tryptophan via the kynurenine and indole pathways is linked to CVD in both CKD and dialysis patients. However, the association between specific kynurenine and indole metabolites with subclinical CVD and time to new cardiovascular (CV) events in CKD has not been studied., Methods: We measured kynurenine and indole pathway metabolites using targeted mass spectrometry in a cohort of 325 patients with moderate to severe CKD and a median follow-up of 2 years. Multiple linear regression and Cox regression analyses were used to assess the relationship between these tryptophan metabolites and subclinical CVD, including calcium scores, carotid intima-media thickness and time to new cardiovascular (CV) events., Results: Elevated quinolinic and anthranilic acids were independently associated with reduced time to new CVD [hazard ratio (HR) 1.28, P  = .01 and HR 1.02, P  = .02, respectively). Low tryptophan levels were associated with reduced time to new CV events when adjusting for demographics and CVD history (HR 0.30, P  = .03). Low tryptophan levels were also associated with aortic calcification in a fully adjusted linear regression model (β = -1983, P  = .006). Similarly, high levels of several kynurenine pathway metabolites predicted increased coronary, aortic and composite calcification scores., Conclusions: We demonstrate the association of kynurenine pathway metabolites, and not indole derivatives, with subclinical and new CV events in an advanced CKD cohort. Our findings support a possible role for altered tryptophan immune metabolism in the pathogenesis of CKD-associated atherosclerosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Purpose: The objective of this study was to investigate the presence of nonbladder sensory abnormalities in participants with overactive bladder syndrome (OAB)., Materials and Methods: Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) study participants with OAB symptoms and controls were recruited from 6 U.S. tertiary referral centers. Quantitative sensory testing (QST) was performed to determine pressure pain sensitivity at the thumbnail bed and auditory sensitivity. Fixed and mixed effect multivariable linear regressions and Weibull models were used to compare QST responses between groups. Pearson correlations were used to assess the relationship between QST measures. Associations between QST and self-reported symptoms were explored with linear regression., Results: A total of 297 participants were analyzed (191 OAB, 106 controls; 76% white, 51% male). OAB cases were older than controls (57.4 vs 52.2 years, p=0.015). No significant differences in experimental thumbnail (nonbladder) pain or auditory sensitivity were detected between OAB cases and controls. Correlations between pressure and auditory derived metrics were weak to moderate overall for both groups, with some significantly stronger correlations for cases. Exploratory analyses indicated increased pressure pain and auditory sensitivity were modestly associated with greater self-reported bladder pain and pain interference with physical function., Conclusions: As a group, no significant differences between OAB cases and controls were observed in experimental nonbladder pain or auditory sensitivity during QST. Associations between QST outcomes and clinical pain raise the possibility of centrally mediated sensory amplification in some individuals with OAB.

Background: In older adults, vision impairment (VI) is associated with worse cognitive function. However, the relationship between midlife vision and future cognitive function remains unknown., Methods: The Study of Women's Health Across the Nation, Michigan site, is a longitudinal cohort of midlife women aged 42-52 years at baseline. Presenting Titmus visual acuity (VA) in the better-seeing eye was assessed at baseline and categorized as no or mild VI (VA ≥20/60), or moderate or worse VI (VA <20/60). Cognitive function was measured 8 times over 15 years using the East Boston Memory Test immediate (EBMTi) and delayed (EBMTd) recall and the Digit Span Backwards (DSB) test. Linear mixed models with a random intercept and slope for age were constructed to detect associations between VI at baseline and future repeated measures of cognitive function, adjusting for age, race, education, financial strain, alcohol use, and tobacco use., Results: About 394 women aged 42-52 at baseline with a maximum follow-up of 20 years were included in this analysis. After covariate adjustment, moderate or worse VI was associated with lower EMBTi (β = -0.56, p = .012), EBMTd (β = -0.60, p = .009), and DSB (β = -0.84, p = .04). While we detected significant associations between VI and levels of cognitive function scores, rates of cognitive decline as individuals aged did not vary by VI status., Conclusion: Moderate or worse VI, assessed during midlife, was associated with lower scores on measures of cognitive function over a 15-year period during which women transitioned from midlife to older adulthood., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To investigate differences across the visual field (VF) in the rate of glaucomatous progression, the likelihood of defect in four disease severity cross-sections, and comparisons of subgroups in each of between 12 demographic, comorbid, and clinical variables., Methods: Two long-term glaucoma clinical trials used Humphrey Field Analyzer 24-2 VFs to calculate pointwise deviations from age-matched normal controls. Slopes of glaucomatous progression over time were calculated per participant using linear mixed models. Pointwise differences between subgroups in slopes and cross-sectional categories were tested, adjusting for multiple comparisons using false discovery rate (FDR) and Q values., Results: Pointwise data were available for 1118 patients who had 15,073 VFs. On average, defects were seen at all VF points. Of the 12 variables, six had average pointwise slopes where Subgroup 1 had significantly faster progression than Subgroup 2 at all or many of the 52 VF points: participants who were older (≥65 vs. younger), 52/52; were male, 13/52; had diabetes, 29/52; had hypertension, 46/52; had a larger cup-to-disc ratio (≥0.7), 36/52; or had larger differences in absolute mean deviation (MD) between eyes (>3 dB), 52/52. Cross-sectional patterns at MD severity of -12 to -6.1 dB showed strong midline effects for gender and other patterns for hypertension, cup-to-disc ratio, absolute difference in MD between eyes, and disc notching., Conclusions: The approach used provides new longitudinal and cross-sectional insights into variation across the VF associated with demographic, comorbid, and clinical variables., Translational Relevance: This exploration and characterization of variable effects in the setting of pointwise VF testing may enable clinicians to anticipate patterns of VF loss based on demographic, comorbid, and clinical associations.

Introduction: measures of vaccine timing require data on vaccination dates, which may be unavailable. This study compares estimates of vaccine coverage and timing; and compares regression techniques that model these measures in the presence of incomplete data., Methods: this cross-sectional study used the 2016 Ethiopian Demographic and Health Survey (DHS), and a 2016 survey from Worabe, Ethiopia. Three measures of vaccine uptake were calculated: coverage (regardless of timing), timeliness (within 1 week of recommended administration), and delay (the number of days between the recommended and actual date of vaccination). Vaccine coverage and timeliness were modeled with logistic regressions. After excluding those without dates, vaccine delay was estimated using linear regression or survival analysis. Vaccine delay was also estimated using accelerated failure time (AFT) models., Results: the DHS survey included 3819 children aged 12-60 months and the Worabe survey included 484 children aged 12-23 months. In the Worabe survey, vaccine coverage for pentavalent vaccine dose 3 was 87.4%, with 8.6% receiving it within 1 week, and 71.7% within 4 weeks; the median delay was 19 days. Predictors of outcomes were similar in both the Worabe survey and Ethiopian DHS, with the largest numbers of significant associations seen in models with vaccine coverage or delays (with AFT models) as the outcomes., Conclusion: estimates of coverage may miss a substantial proportion of infants who have delayed vaccination. Accelerated failure time (AFT) models are useful to estimate vaccine delay because they include information from all respondents (those with full and partial data on vaccination dates) and are agnostic about an age limit for timely vaccination., Competing Interests: The authors declare no competing interests., (Copyright: Abram Luther Wagner et al.)

Purpose: To assess whether routine fundus photography (RFP) to screen for posterior segment disease at community eye clinics (vision centers [VCs]) in India increases referral to centralized ophthalmolic care., Design: Stepped-wedge, cluster-randomized trial., Participants: Patients aged 40 to 75 years and those aged 20 to 40 years with a known history of hypertension or diabetes mellitus presenting to 4 technician-run VCs associated with the Aravind Eye Care System in India., Methods: VCs (clusters) were randomized to standard care or RFP across five 2-week study periods (steps). Patients in each cluster received standard care initially. At the start of each subsequent step, a randomly chosen cluster crossed over to providing RFP to eligible patients. All clusters took part in RFP during the last step. Standard care involved technician eye exams, optional fundus photography, and teleconsultation with an ophthalmologist. RFP involved eye exams, dilation and 40-degree fundus photography, and teleconsultation with an ophthalmologist., Main Outcome Measures: Standard care and RFP clusters were compared by the proportion of patients referred for in-person evaluation by an ophthalmologist because of fundus photography findings and urgency of referral (urgently in ≤ 2 weeks vs. nonurgently in > 2 weeks). Generalized linear mixed models adjusting for cluster and step were used to estimate the odds of referral due to fundus photography findings compared with standard care., Results: A total of 1447 patients were enrolled across the VCs, including 737 in the standard care group and 710 in the RFP group. Compared with standard care, the RFP group had a higher proportion of referrals due to fundus photography findings (11.3% vs. 4.4%), nonurgent referrals due to fundus photography (9.3% vs. 3.3%), and urgent referrals due to fundus photography (1.8% vs. 1.1%). The RFP intervention was associated with a 2-fold increased odds of being referred because of photography findings compared with standard care (odds ratio, 2.07; 95% confidence interval, 0.98-4.40; P = 0.058)., Conclusions: Adding RFP to community eye clinics was associated with an increased odds of referral compared with standard care. This increase in referral was mostly due to nonurgent posterior segment disease., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Kidney disease is a common, complex, costly, and life-limiting condition. Most kidney disease registries or information systems have been limited to single institutions or regions. A national US Department of Veterans Affairs (VA) Renal Information System (VA-REINS) was recently developed. We describe its creation and present key initial findings related to chronic kidney disease (CKD) without kidney replacement therapy (KRT). Data from the VA's Corporate Data Warehouse were processed and linked with national Medicare data for patients with CKD receiving KRT. Operational definitions for VA user, CKD, acute kidney injury, and kidney failure were developed. Among 7 million VA users in fiscal year 2014, CKD was identified using either a strict or liberal operational definition in 1.1 million (16.4%) and 2.5 million (36.3%) veterans, respectively. Most were identified using an estimated glomerular filtration rate laboratory phenotype, some through proteinuria assessment, and very few through International Classification of Diseases, Ninth Revision coding. The VA spent ∼$18 billion for the care of patients with CKD without KRT, most of which was for CKD stage 3, with higher per-patient costs by CKD stage. VA-REINS can be leveraged for disease surveillance, population health management, and improving the quality and value of care, thereby enhancing VA's capacity as a patient-centered learning health system for US veterans., (Copyright © 2020. Published by Elsevier Inc.)

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., Competing Interests: HT is a consultant to Otsuka and Chemocentryx (Data Monitoring Committees) and receives support from Travere Therapeutic and Goldfinch BioPharma Inc. through separate grants to 10.13039/100006732New York University. In addition, he has received research support from Natera Inc. LAG receives research support from 10.13039/100011022Vertex Pharmaceuticals and Reata Pharmaceuticals. SEW has a consulting agreement with Bristol-Myers Squibb. The remaining authors declare no perceived or actual COIs., (© 2021 Published by Elsevier Inc.)

Background/aims: Obesity is a known risk factor for cardiovascular disease and contributes to the development and progression of kidney disease. However, the specific influence of obesity on outcomes in primary glomerular disease has not been well characterized., Methods: In this prospective cohort study, data were from 541 participants enrolled in the Nephrotic Syndrome Study Network (NEPTUNE), between 2010 and 2019, at 23 sites across North America. Blood pressure, lipids, and kidney disease outcomes including complete proteinuria remission, kidney failure, and chronic kidney disease progression were evaluated. Data were analyzed using linear and logistic regression with generalized estimating equations and time-varying Cox regression with Kaplan-Meier plots., Results: The prevalence of obesity at baseline was 43.3% (N = 156) in adults and 37.6% (N = 68) in children. In adults, obesity was longitudinally associated with higher systolic BP (β = 6.49, 95% CI: 2.41, 10.56, p = 0.002), dyslipidemia (OR = 1.74, 95% CI: 1.30, 2.32, p < 0.001), triglycerides (β = 41.92, 95% CI: 17.12, 66.71, p = 0.001), and lower HDL (β = -6.92, 95% CI: -9.32, -4.51, p < 0.001). In children, obesity over time was associated with higher systolic BP index (β = 0.04, 95% CI: 0.02, 0.06, p < 0.001) and hypertension (OR = 1.43, 95% CI: 1.04, 1.98, p = 0.03). In both adults and children, obesity was associated with a significantly lower hazard of achieving complete remission of proteinuria (adult HR = 0.80, 95% CI: 0.69, 0.88, p < 0.001; pediatric HR = 0.72, 95% CI: 0.61, 0.84, p < 0.001)., Conclusion: Obesity was associated with higher cardiovascular risk and less proteinuria remission from nephrotic syndrome in adults and children with proteinuric glomerulopathies. Weight-loss strategies may forestall cardiovascular disease and progressive kidney function decline in this high-risk patient group., (© 2021 S. Karger AG, Basel.)

Aims: Measurement of self-reported lower urinary tract symptoms (LUTS) typically uses a recall period, for example, "In the past 30 days…." Compared to averaged daily reports, 30-day recall is generally unbiased, but recall bias varies by item. We examined the associations between personal characteristics (eg, age, symptom bother) and 30-day recall of LUTS using items from the Symptoms of Lower Urinary Tract Dysfunction Research Network Comprehensive Assessment of Self-reported Urinary Symptoms questionnaire., Methods: Participants (127 women and 127 men) were recruited from 6 US tertiary care sites. They completed daily assessments for 30 days and a 30-day recall assessment at the end of the study month. For each of the 18 tested items, representing 10 LUTS, the average of the participant's daily responses was modeled as a function of their 30-day recall, the personal characteristic, and the interaction between the 30-day recall and the characteristic in separate general linear regression models, adjusted for sex., Results: Nine items representing 7 LUTS exhibited under- or overreporting (recall bias) for at least 25% of participants. Bias was associated with personal characteristics for six LUTS. Underreporting of incontinence was associated with older age, lower anxiety, and negative affect; overreporting of other LUTS was associated with, symptom bother, symptom variability, anxiety, and depression., Conclusions: We identified under- or overreporting that was associated with personal characteristics for six common LUTS. Some cues (eg, less bother and lower anxiety) were related to recall bias in an unexpected direction. Thus, providers should exercise caution when making judgments about the accuracy of a patient's symptom recall based on patient demographic and psychosocial characteristics., (© 2020 Wiley Periodicals LLC.)

Rationale & Objective: Persons with chronic kidney disease (CKD) are often unaware of their disease status. Efforts to improve CKD awareness may be most effective if focused on persons at highest risk for progression to kidney failure., Study Design: Serial cross-sectional surveys., Setting & Participants: Nonpregnant adults (aged≥20 years) with CKD glomerular filtration rate categories 3-4 (G3-G4) who participated in the National Health and Nutrition Examination Survey from 1999 to 2016 (n = 3,713)., Predictor: 5-year kidney failure risk, estimated using the Kidney Failure Risk Equation. Predicted risk was categorized as minimal (<2%), low (2%-<5%), intermediate (5%-<15%), or high (≥15%)., Outcome: CKD awareness, defined by answering "yes" to the question "Have you ever been told by a doctor or other health professional that you had weak or failing kidneys?", Analytical Approach: Prevalence of CKD awareness was estimated within each risk group using complex sample survey methods. Associations between Kidney Failure Risk Equation risk and CKD awareness were assessed using multivariable logistic regression. CKD awareness was compared with awareness of hypertension and diabetes during the same period., Results: In 2011 to 2016, unadjusted CKD awareness was 9.6%, 22.6%, 44.7%, and 49.0% in the minimal-, low-, intermediate-, and high-risk groups, respectively. In adjusted analyses, these proportions did not change over time. Awareness of CKD, including among the highest risk group, remains consistently below that of hypertension and diabetes and awareness of these conditions increased over time., Limitations: Imperfect sensitivity of the "weak or failing kidneys" question for ascertaining CKD awareness., Conclusions: Among adults with CKD G3-G4 who have 5-year estimated risks for kidney failure of 5%-<15% and≥15%, approximately half were unaware of their kidney disease, a gap that has persisted nearly 2 decades., (Copyright © 2020 National Kidney Foundation, Inc. All rights reserved.)

Importance: The overall prevalence of chronic kidney disease (CKD) has stabilized in the United States in recent years. However, it is unclear whether all major sociodemographic groups experienced this trend., Objective: To examine trends in CKD prevalence across major sociodemographic groups as defined by race/ethnicity and socioeconomic status., Design, Setting, and Participants: This repeated cross-sectional study used data from the National Health and Nutrition Examination Surveys for 1988 to 1994 and every 2 years from 1999 to 2016 on individuals 20 years or older with information on race/ethnicity, socioeconomic status, and serum creatinine levels. Statistical analysis was conducted from May 1, 2017, to April 6, 2020., Exposures: Race/ethnicity and socioeconomic status., Main Outcomes and Measures: Prevalence of CKD was defined as an estimated glomerular filtration rate of 15 to 59 mL/min/1.73 m2., Results: A total of 54 554 participants (mean [SE] age, 46.2 [0.2] years; 51.7% female) were examined. The age-, sex- and race/ethnicity-adjusted overall prevalence of stage 3 and 4 CKD increased from 3.9% in 1988-1994 to 5.2% in 2003-2004 (difference, 1.3%; 95% CI, 0.9%-1.7%; P < .001 for change) and remained relatively stable thereafter at 5.1% in 2015-2016 (difference, -0.1%; 95% CI, -0.7% to 0.4%; P = .61 for change). The trend in adjusted CKD prevalence differed significantly by race/ethnicity (P = .009 for interaction). In non-Hispanic white and non-Hispanic black persons, CKD prevalence increased between 1988-1994 and 2003-2004 and remained stable thereafter. Among Mexican American persons, CKD prevalence was lower than in other racial/ethnic groups and remained stable between 1988-1994 and 2003-2004 but nearly doubled (difference, 2.1%; 95% CI, 0.9%-3.3%; P = .001 for change) between 2003-2004 and 2015-2016 to rates similar to those in other racial/ethnic groups. There were higher rates of CKD prevalence among groups with lower educational level and income (eg, 5.8% vs 4.3% and 4.3% vs 3.1% in low vs high education and income, respectively, in 1988-1994), but trends in CKD prevalence mirrored those for the overall population. The higher CKD prevalence among individuals with lower educational level and income remained largely consistent throughout the entire period. Results were similar in most subgroups when including albuminuria to define CKD., Conclusions and Relevance: The prevalence of CKD in the United States has stabilized overall in recent years but has increased among Mexican American persons. More important, gaps in CKD prevalence across racial/ethnic groups and levels of socioeconomic status largely persisted over 28 years. There is a need to identify and address causes of increasing CKD prevalence among Mexican American persons and a need to renew efforts to effectively mitigate persistent disparities in CKD prevalence.

Rationale & Objective: Surrogate outcomes for end-stage kidney disease often assume linear changes, which may not reflect true estimated glomerular filtration rate (eGFR) trajectories. This study's objective was to characterize nonlinear eGFR trajectories in nephrotic syndrome., Study Design: Observational cohort study., Setting & Participants: Nephrotic Syndrome Study Network (NEPTUNE) is a multicenter study of adult and pediatric patients with proteinuria enrolled at clinically indicated kidney biopsy or initial presentation of disease (pediatric only)., Predictors: Patient demographic, clinical, and pathology variables at study enrollment and follow-up time., Outcome: eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (patients ≥ 18 years old) or modified Chronic Kidney Disease in Children Study-Schwartz (patients < 18 years) formulas. The probability of nonlinearity (PNL) was calculated for individual eGFR trajectories., Analytical Approach: Associations between predictors and PNL were assessed using multivariable linear regression., Results: 453 patients with ≥3 eGFR measurements and 1 or more year of follow-up were included (median follow-up, 3.6 years). Median PNL was 0.052; 56% and 16% had PNL < 10% and >50%, respectively. In both adults and pediatric patients, higher baseline eGFR was associated with higher PNL, whereas longer follow-up time was associated with lower PNL. Higher urine protein-creatinine ratio and steroid use were also associated with higher PNL in adults. Higher percentages of tubular atrophy and foot-process effacement were associated with lower and higher PNLs, respectively, in adults., Limitations: Relatively short follow-up time, inability to assess acute kidney injury events, and variable eGFR measurement frequency across patients., Conclusions: Although increasing follow-up time resulted in more linear trajectories, nonlinear eGFR trajectories were common in this cohort. Future studies in nephrotic syndrome should consider novel outcomes that do not rely on linearity assumptions., (© 2020 The Authors.)

Background: To better understand the relation between sleep problems and CKD, we examined temporal trends in the prevalence of self-reported sleep problems in adults in the United States and their associations with CKD and all-cause mortality., Methods: Using data from 27,365 adult participants in five biannual National Health and Examination Surveys (2005-2006 through 2013-2014), we studied five self-reported sleep problems-trouble sleeping, sleep disorder, nocturia (urinating ≥2 times/night), inadequate sleep (<7 hours/night), and excessive sleep (>9 hours/night)-plus a composite index. We conducted three types of analysis: temporal trends in the prevalence of each sleep measure by CKD status, using model-based standardization; cross-sectional analysis of associations between four CKD measures and each sleep measure, using logistic regression; and survival analysis of the association between each sleep measure and mortality, using Cox regression., Results: The prevalence of trouble sleeping and sleep disorder increased over the five surveys by 4% and 3%, respectively, whereas the other sleep problems remained relatively stable. All sleep problems, except inadequate sleep, were more common during the study period among adults with CKD than without CKD (40% versus 21% for nocturia; 5% versus 2% for excessive sleep; 30% versus 25% for trouble sleeping; 12% versus 8% for sleep disorder). Both eGFR <30 ml/min per 1.73 m 2 and albuminuria were positively associated with nocturia and excessive sleep. Excessive sleep and nocturia were also associated with higher mortality (adjusted hazard ratio for >9 versus 7-9 hours/night=1.7; 95% CI, 1.3 to 2.1; and for nocturia=1.2; 95% CI, 1.1 to 1.4)., Conclusions: The high prevalence of sleep problems among persons with CKD and their associations with mortality suggest their potential importance to clinical practice. Future work could examine the health effects of identifying and treating sleep problems in patients with CKD., Competing Interests: H. Morgenstern has been a consultant at Arbor Research Collaborative for Health. All remaining authors have nothing to disclose., (Copyright © 2020 by the American Society of Nephrology.)

Background: The analysis and reporting of glomerular features ascertained by electron microscopy are limited to few parameters with minimal predictive value, despite some contributions to disease diagnoses., Methods: We investigated the prognostic value of 12 electron microscopy histologic and ultrastructural changes (descriptors) from the Nephrotic Syndrome Study Network (NEPTUNE) Digital Pathology Scoring System. Study pathologists scored 12 descriptors in NEPTUNE renal biopsies from 242 patients with minimal change disease or FSGS, with duplicate readings to evaluate reproducibility. We performed consensus clustering of patients to identify unique electron microscopy profiles. For both individual descriptors and clusters, we used Cox regression models to assess associations with time from biopsy to proteinuria remission and time to a composite progression outcome (≥40% decline in eGFR, with eGFR<60 ml/min per 1.73 m 2 , or ESKD), and linear mixed models for longitudinal eGFR measures., Results: Intrarater and interrater reproducibility was >0.60 for 12 out of 12 and seven out of 12 descriptors, respectively. Individual podocyte descriptors such as effacement and microvillous transformation were associated with complete remission, whereas endothelial cell and glomerular basement membrane abnormalities were associated with progression. We identified six descriptor-based clusters with distinct electron microscopy profiles and clinical outcomes. Patients in a cluster with more prominent foot process effacement and microvillous transformation had the highest rates of complete proteinuria remission, whereas patients in clusters with extensive loss of primary processes and endothelial cell damage had the highest rates of the composite progression outcome., Conclusions: Systematic analysis of electron microscopic findings reveals clusters of findings associated with either proteinuria remission or disease progression., (Copyright © 2020 by the American Society of Nephrology.)

Purpose: To evaluate the relationship between medication adherence and visual field progression in participants randomized to the medication arm of the Collaborative Initial Glaucoma Treatment Study (CIGTS)., Design: The CIGTS was a randomized, multicenter clinical trial comparing initial treatment with topical medications to trabeculectomy for 607 participants with newly diagnosed glaucoma., Participants: Three hundred seven participants randomized to the medication arm of the CIGTS., Methods: Participants were followed up at 6-month intervals for up to 10 years. Self-reported medication adherence and visual fields were measured. Medication adherence was assessed by telephone from responses to the question, "Did you happen to miss any dose of your medication yesterday?" The impact of medication adherence on mean deviation (MD) over time was assessed with a linear mixed regression model adjusting for the effects of baseline MD and age, cataract extraction, interactions, and time (through year 8, excluding time after crossover to surgery). Medication adherence was modeled as a cumulative sum of the number of prior visits where a missed dose of medication was reported., Main Outcome Measure: Mean deviation over time., Results: Three hundred seven subjects (306 with adherence data) were randomized to treatment with topical medications and followed up for an average of 7.3 years (standard deviation, 2.3 years). One hundred forty-two subjects (46%) reported never missing a dose of medication over all available follow-up, 112 patients (37%) reported missing medication at up to one third of visits, 31 patients (10%) reported missing medication at one third to two thirds of visits, and 21 patients (7%) reported missing medication at more than two thirds of visits. Worse medication adherence was associated with loss of MD over time (P = 0.005). For subjects who reported never missing a dose of medication, the average predicted MD loss over 8 years was 0.62 dB, consistent with age-related loss (95% confidence interval [CI], 0.17-1.06; P = 0.007); subjects who reported missing medication doses at one third of visits had a loss of 1.42 dB (95% CI, 0.86-1.98; P < 0.0001); and subjects who reported missing medication doses at two thirds of visits showed a loss of 2.23 dB (95% CI, 1.19-3.26; P < 0.0001)., Conclusions: This longitudinal assessment demonstrated a statistically and clinically significant association between medication nonadherence and glaucomatous vision loss., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)