Albuminuria, Hypertension, and Reduced Kidney Volumes in Adolescents Born Extremely Premature

Background: Premature birth is associated with decreased nephron number and an increased risk for chronic kidney disease (CKD). To inform the development of guidelines for kidney follow up of children born prematurely, we undertook a study of individuals born extremely preterm, with the aim of characterizing the prevalence and predictors of microalbuminuria, elevated blood pressure, and/or abnormal kidney volume in adolescence. Methods: Study participants (n = 42) were born before 28 weeks of gestation and were enrolled at birth in the Extremely Low Gestational Age Newborns (ELGAN) study. When participants were 15 years old, we obtained 2 manual blood pressures, a spot urine microalbumin measurement, and sonographic measurements of kidney length and volume. Results: Of the 42 participants, 60% were male, 52% were Caucasian (18% Hispanic), and 43% were African-American. Their median age was 15 (IQR 15, 15.3) years. In 33.3% of the cohort, blood pressure was elevated (>120/80 mmHg). Microalbuminuria (>30 mg/g) was present in 11.9% of the cohort, and kidney volume below the 10th percentile of normative data was present in 14%. Twenty-one (50%) of the sample had at least one kidney abnormality (microalbuminuria, elevated blood pressures, and/or kidney hypoplasia); these individuals were more likely to have experienced neonatal hypotension [55% vs. 17% among those with no kidney abnormality, p = 0.02]. Conclusions: Half of adolescents in this subset of ELGAN cohort have at least one risk factor of kidney disease (reduced kidney volume, microalbuminuria, and/or elevated blood pressures) at 15 years of age. This study suggests the importance of monitoring kidney outcomes in children after extremely preterm birth, especially those with a history of neonatal hypotension

America's Rural Hospitals: A Selective Review of 1980s Research

We review 1980s research on American rural hospitals within the context of a decade of increasing restrictiveness in the reimbursement and operating environments. Areas addressed include rural hospital definitions, organizational and financial performance, and strategic management activities. The latter category consists of hospital closure, diversification and vertical integration, swing-bed conversion, sole community provider designation, horizontal integration and multihospital system affiliation, marketing, and patient retention. The review suggests several research needs, including: developing more meaningful definitions of rural hospitals, engaging in methodologically sound work on the effects of innovative programs and strategic management activities—including conversion of the facility itself—on rural hospital performance, and completing studies of the effects of rural hospital closure or conversion on the health of the communities served.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74857/1/j.1748-0361.1990.tb00682.x.pd

APOL1 genotype-associated morphologic changes among patients with focal segmental glomerulosclerosis

Background: The G1 and G2 alleles of apolipoprotein L1 (APOL1) are common in the Black population and associated with increased risk of focal segmental glomerulosclerosis (FSGS). The molecular mechanisms linking APOL1 risk variants with FSGS are not clearly understood, and APOL1’s natural absence in laboratory animals makes studying its pathobiology challenging. Methods: In a cohort of 90 Black patients with either FSGS or minimal change disease (MCD) enrolled in the Nephrotic Syndrome Study Network (58% pediatric onset), we used kidney biopsy traits as an intermediate outcome to help illuminate tissue-based consequences of APOL1 risk variants and expression. We tested associations between APOL1 risk alleles or glomerular APOL1 mRNA expression and 83 light- or electron-microscopy traits measuring structural and cellular kidney changes. Results: Under both recessive and dominant models in the FSGS patient subgroup (61%), APOL1 risk variants were significantly correlated (defined as FDR <0.1) with decreased global mesangial hypercellularity, decreased condensation of cytoskeleton, and increased tubular microcysts. No significant correlations were detected in MCD cohort. Independent of risk alleles, glomerular APOL1 expression in FSGS patients was not correlated with morphologic features. Conclusions: While APOL1-associated FSGS is associated with two risk alleles, both one and two risk alleles are associated with cellular/tissue changes in this study of FSGS patients. Our lack of discovery of a large group of tissue differences in FSGS and no significant difference in MCD may be due to the lack of power but also supports investigating whether machine learning methods may more sensitively detect APOL1-associated changes

Complete remission in the nephrotic syndrome study network

Background and objectives This analysis from the Nephrotic Syndrome Study Network (NEPTUNE) assessed the phenotypic and pathology characteristics of proteinuric patients undergoing kidney biopsy and defined the frequency and factors associated with complete proteinuria remission (CRever). Design, setting, participants, &amp; measurements We enrolled adults and children with proteinuria ≥0.5 g/d at the time of first clinically indicated renal biopsy at 21 sites in North America from April 2010 to June 2014 into a prospective cohort study. NEPTUNE central pathologists assigned participants to minimal-change disease (MCD), FSGS, membranous nephropathy, or other glomerulopathy cohorts. Outcome measures for this analysis were (1) CRever with urine protein-to-creatinine ratio (UPC)&lt;0.3 g/g with preserved native kidney function and (2) ESRD. Continuous variables are reported as median and interquartile range (IQR; 25th, 75th percentile). Cox proportional hazards modeling was used to assess factors associated with CRever. Results We enrolled 441 patients: 116 (27%) had MCD, 142 (32%) had FSGS, 66 (15%) had membranous nephropathy, and 117 (27%) had other glomerulopathy. The baseline UPC was 4.1 g/g (IQR, 1.9, 7.7) and the eGFR was 81 ml/min per 1.73 m2 (IQR, 50, 105). Median duration of observation was 19 months (IQR, 11, 30). CRever occurred in 46% of patients, and 4.6% progressed to ESRD. Multivariate analysis demonstrated that higher prebiopsy proteinuria (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.5) and pathology diagnosis (FSGS versus MCD; hazard ratio, 0.2; 95% confidence interval, 0.1 to 0.5) were inversely associated with CRever. The effect of immunosuppressive therapy on remission varied by pathology diagnosis. Conclusions In NEPTUNE, the high frequency of other pathology in proteinuric patients affirms the value of the diagnostic kidney biopsy. Clinical factors, including level of proteinuria before biopsy, pathology diagnosis, and immunosuppression, are associated with complete remission

The longitudinal relationship between patient-reported outcomes and clinical characteristics among patients with focal segmental glomerulosclerosis in the nephrotic syndrome study network

Background. Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS). Methods. FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied. Results. There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (-7.6 points, P ¼ 0.02) and mobility (-4.2, P ¼ 0.02), the number of reported symptoms was associated with worse depression (-2.7 per symptom, P ¼ 0.009) and anxiety (-2.3, P ¼ 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (-2.8 per visit, P < 0.001) and fatigue (-2.4, P ¼ 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (þ9.3, P ¼ 0.03). Conclusions. PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes