Trends Associated With Large-scale Expansion of Peritoneal Dialysis Within an Integrated Care Delivery Model.

IMPORTANCE: Despite favorable national trends in the incidence of end-stage renal disease (ESRD) from 2008 to 2011, ESRD incidence has been increasing recently, and less than 10% of patients with ESRD start renal replacement therapy with peritoneal dialysis (PD) in the United States. Given known and potential advantages of PD over hemodialysis, the Kaiser Permanente Northern California integrated health care delivery system implemented a program to expand use of PD. OBJECTIVES: To describe the system-level approach to expansion of PD use and temporal trends in initiation and persistence of PD and its associated mortality. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included adult members of a large integrated health care delivery system in Northern California who initiated chronic dialysis therapy from January 1, 2008, through December 31, 2018. Data were analyzed from March 1, 2018, through May 31, 2019. EXPOSURE: From 2008 to 2018, Kaiser Permanente Northern California implemented a multidisciplinary, system-wide approach to increase use of PD that included patient and caregiver education, education and support tools for health care professionals, streamlined system-level processes, monitoring, and continuous quality improvement. MAIN OUTCOMES AND MEASURES: Temporal trends in the proportion of patients starting chronic dialysis with PD vs hemodialysis compared with national trends. Secondary outcomes included persistence of PD at 1 year in those initiating it and standardized 1-year mortality rates in those initiating PD or hemodialysis. RESULTS: Among 13 500 eligible health plan members in the study population (7840 men [58.1%] and 5660 women [41.9%]; mean [SD] age, 64.3 [14.4] years), initiation of PD increased from 165 of 1089 all new dialysis patients (15.2%) in 2008 to 486 of 1438 (33.8%) in 2018, which was substantially higher than national trends (6.1% in 2008 and 9.7% in 2016). Among the 2974 patients who initiated PD from 2008 to 2017, 2387 (80.3%) continued PD at 1 year after initiation, with a significant increase in age-, sex-, and race-standardized rates from 2008 (69.1%) to 2017 (84.2%). Age-, sex-, and race-standardized 1-year mortality for patients receiving PD and hemodialysis did not change significantly across this 10-year period (17.3% to 15.5% for hemodialysis, P = 0.89 for trend; and 5.5% to 7.3% for PD, P = 0.12 for trend). CONCLUSIONS AND RELEVANCE: This study suggests that large-scale expansion of PD is feasible using a multidisciplinary, integrated, coordinated care approach; we believe these findings represent a national opportunity to improve outcomes for patients with advanced kidney disease.

SRC-1 Regulates Blood Pressure and Aortic Stiffness in Female Mice.

Framingham Heart Study suggests that dysfunction of steroid receptor coactivator-1 may be involved in the development of hypertension. However, there is no functional evidence linking steroid receptor coactivator-1 to the regulation of blood pressure. We used immunohistochemistry to map the expression of steroid receptor coactivator-1 protein in mouse brain, especially in regions implicated in the regulation of blood pressure. Steroid receptor coactivator-1 protein was found in central amygdala, medial amygdala, supraoptic nucleus, arcuate nucleus, ventromedial, dorsomedial, paraventricular hypothalamus, and nucleus of the solitary tract. To determine the effects of steroid receptor coactivator-1 protein on cardiovascular system we measured blood pressures, blood flow velocities, echocardiographic parameters, and aortic input impedance in female steroid receptor coactivator-1 knockout mice and their wild type littermates. Steroid receptor coactivator-1 knockout mice had higher blood pressures and increased aortic stiffness when compared to female wild type littermates. Additionally, the hearts of steroid receptor coactivator-1 knockout mice seem to consume higher energy as evidenced by increased impedance and higher heart rate pressure product when compared to female wild type littermates. Our results demonstrate that steroid receptor coactivator-1 may be functionally involved in the regulation of blood pressure and aortic stiffness through the regulation of sympathetic activation in various neuronal populations.

Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism.

BACKGROUND: Certain loci on the human genome, such as glutathione S-transferase M1 (GSTM1), do not permit heterozygotes to be reliably determined by commonly used methods. Association of such a locus with a disease is therefore generally tested with a case-control design. When subjects have already been ascertained in a case-parent design however, the question arises as to whether the data can still be used to test disease association at such a locus. RESULTS: A likelihood ratio test was constructed that can be used with a case-parents design but has somewhat less power than a Pearson's chi-squared test that uses a case-control design. The test is illustrated on a novel dataset showing a genotype relative risk near 2 for the homozygous GSTM1 deletion genotype and autism. CONCLUSION: Although the case-control design will remain the mainstay for a locus with a deletion, the likelihood ratio test will be useful for such a locus analyzed as part of a larger case-parent study design. The likelihood ratio test has the advantage that it can incorporate complete and incomplete case-parent trios as well as independent cases and controls. Both analyses support (p = 0.046 for the proposed test, p = 0.028 for the case-control analysis) an association of the homozygous GSTM1 deletion genotype with autism.

Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders.

OBJECTIVE: To evaluate an association between cytokine production with common dietary proteins as a marker of non-allergic food hypersensitivity (NFH) and gastrointestinal (GI) symptoms in young children with autism spectrum disorders (ASD). STUDY DESIGN: Peripheral blood mononuclear cells (PBMCs) were obtained from 109 ASD children with or without GI symptoms (GI [+] ASD, N = 75 and GI (-) ASD, N = 34], from children with NFH (N = 15), and control subjects (N = 19). Diarrhea and constipation were the major GI symptoms. We measured production of type 1 T-helper cells (Th1), type 2 T-helper cells (Th2), and regulatory cytokines by PBMCs stimulated with whole cow's milk protein (CMP), its major components (casein, beta-lactoglobulin, and alpha-lactoalbumin), gliadin, and soy. RESULTS: PBMCs obtained from GI (+) ASD children produced more tumor necrosis factor-alpha (TNF-alpha)/interleukin-12 (IL-12) than those obtained from control subjects with CMP, beta-lactoglobulin, and alpha-lactoalbumin, irrespective of objective GI symptoms. They also produced more TNF-alpha with gliadin, which was more frequently observed in the group with loose stools. PBMCs obtained from GI (-) ASD children produced more TNF-alpha/IL-12 with CMP than those from control subjects, but not with beta-lactoglobulin, alpha-lactoalbumin, or gliadin. Cytokine production with casein and soy were unremarkable. CONCLUSION: A high prevalence of elevated TNF-alpha/IL-12 production by GI (+) ASD PBMCs with CMP and its major components indicates a role of NFH in GI symptoms observed in children with ASD.

Recovery from osteoporosis through skeletal growth: early bone mass acquisition has little effect on adult bone density.

It is often assumed that bone mineral accretion should be optimized throughout childhood to maximize peak bone mass. In contrast, we hypothesized that bone mineral acquisition early in life would have little or no effect on adult bone mass because many areas of the juvenile skeleton are replaced in toto through skeletal growth. To test this hypothesis, we induced osteoporosis by administering dexamethasone to 5-week-old rabbits for 5 weeks and then allowed them to recover for 16 weeks. Tibial bone mineral density (ash weight/volume) was decreased in the dexamethasone-treated animals at the end of treatment but recovered completely. Bone structure in the femur was assessed by histomorphometry. Trabecular and cortical bone in the distal metaphysis was made osteoporotic by dexamethasone, but was then replaced through endochondral bone formation and recovered. Periosteal bone formation rate in the diaphysis was decreased during dexamethasone treatment but afterwards rebounded above controls and normalized cortical width. Our data suggest that bone mineral acquisition early in life has little effect on adult bone density because the juvenile bone is largely replaced through growth. If this concept generalizes, then interventions to maximize peak bone mass should be directed at adolescents rather than young children.