Long-Term Outcomes in Nephrotic Syndrome by Kidney Biopsy Diagnosis and Proteinuria.

Key Points: In nephrotic syndrome, diagnosis was associated with kidney failure risk: very high in monogenic cases, substantial in FSGS, and less but not zero in minimal change disease. Early control of proteinuria was associated with lower kidney failure risk, and in FSGS levels <1.5 g/g are associated with good kidney outcomes at 10 years.

Long-term outcomes of patients with IgA nephropathy in the German CKD cohort.

Background: The importance of albuminuria as opposed to proteinuria in predicting kidney outcomes in primary immunoglobulin A nephropathy (IgAN) is not well established.

Methods: From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the German Chronic Kidney Disease (GCKD) cohort, a prospective observational cohort study ( = 5217). Adjudicated endpoints include a composite kidney endpoint (CKE) consisting of eGFR decline >40%, eGFR <15 ml/min/1.

Long-Term Outcomes in IgA Nephropathy.

Background: IgA nephropathy can progress to kidney failure, and risk assessment soon after diagnosis has advantages both for clinical management and the development of new therapeutics. We present relationships among proteinuria, eGFR slope, and lifetime risks for kidney failure.

Methods: The IgA nephropathy cohort (2299 adults and 140 children) of the UK National Registry of Rare Kidney Diseases (RaDaR) was analyzed.

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial.

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety.

Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries.

Association of Treatment Effects on Early Change in Urine Protein and Treatment Effects on GFR Slope in IgA Nephropathy: An Individual Participant Meta-analysis.

Rationale & Objective: An early change in proteinuria is considered a reasonably likely surrogate end point in immunoglobulin A nephropathy (IgAN) and can be used as a basis for accelerated approval of therapies, with verification in a postmarketing confirmatory trial. Glomerular filtration rate (GFR) slope is a recently validated surrogate end point for chronic kidney disease progression and may be considered as the end point used for verification. We undertook a meta-analysis of clinical trials in IgAN to compare treatment effects on change in proteinuria versus change in estimated GFR (eGFR) slope.

Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial.

Background: IgA nephropathy is thought to be associated with mucosal immune system dysfunction, which manifests as renal IgA deposition that leads to impairment and end-stage renal disease in 20-40% of patients within 10-20 years. In this trial (NEFIGAN) we aimed to assess safety and efficacy of a novel targeted-release formulation of budesonide (TRF-budesonide), designed to deliver the drug to the distal ileum in patients with IgA nephropathy.

Methods: We did a randomised, double-blind, placebo-controlled phase 2b trial, comprised of 6-month run-in, 9-month treatment, and 3-month follow-up phases at 62 nephrology clinics across ten European countries.

Early Change in Urine Protein as a Surrogate End Point in Studies of IgA Nephropathy: An Individual-Patient Meta-analysis.

Background: The role of change in proteinuria as a surrogate end point for randomized trials in immunoglobulin A nephropathy (IgAN) has previously not been thoroughly evaluated.

Study Design: Individual patient-level meta-analysis.

Setting & Population: Individual-patient data for 830 patients from 11 randomized trials evaluating 4 intervention types (renin-angiotensin system [RAS] blockade, fish oil, immunosuppression, and steroids) examining associations between changes in urine protein and clinical end points at the individual and trial levels.

Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson's disease.

We investigated the effects of exendin-4 on neural stem/progenitor cells in the subventricular zone of the adult rodent brain and its functional effects in an animal model of Parkinson's disease. Our results showed expression of GLP-1 receptor mRNA or protein in the subventricular zone and cultured neural stem/progenitor cells isolated from this region. In vitro, exendin-4 increased the number of neural stem/progenitor cells, and the number of cells expressing the neuronal markers microtubule-associated protein 2, beta-III-tubulin, and neuron-specific enolase.

Sexual risk behavior of married men and women in Bangladesh associated with husbands' work migration and living apart.

Objectives: This study aimed to ascertain the prevalence of sexual risk behavior among married men and women who had, or had not, lived apart from their spouse as a result of the husbands' work migration.

Methods: A cross-sectional survey was conducted among a random sample of 1,175 married women and 703 married men in 2 rural areas of Bangladesh.

Results: Extramarital sex was reported by 64.

Risk factors for neonatal mortality in rural areas of Bangladesh served by a large NGO programme.

Neonatal deaths account for about half of all deaths among children under 5 years of age in Bangladesh, making prevention a major priority. This paper reports on a study of neonatal deaths in 12 areas of Bangladesh served by a large NGO programme, which had high coverage of reproductive health outreach services and relatively low neonatal mortality in recent years. The study aimed to identify the main factors associated with neonatal mortality in these areas, with a view to developing appropriate strategies for prevention.

Use of family planning services in the transition to a static clinic system in Bangladesh: 1998-2002.

Context: In rural Bangladesh, family planning services--previously provided through household visits and satellite clinics--were transferred to static community clinics under the government's sectoral program for 1998-2003, but the next sectoral program reversed the change without a formal evaluation. It is important to assess changes in utilization and coverage to inform further development of the service delivery system.

Methods: Longitudinal data on use of family planning services and contraceptive methods were collected quarterly in 1998-2002 from married women in about 11,000 households in two rural surveillance areas--Abhoynagar and Mirsarai.

Epidermal growth factor (EGF) withdrawal masks gene expression differences in the study of pituitary adenylate cyclase-activating polypeptide (PACAP) activation of primary neural stem cell proliferation.

Background: The recently discovered adult neural stem cells, which maintain continuous generation of new neuronal and glial cells throughout adulthood, are a promising and expandable source of cells for use in cell replacement therapies within the central nervous system. These cells could either be induced to proliferate and differentiate endogenously, or expanded and differentiated in culture before being transplanted into the damaged site of the brain. In order to achieve these goals effective strategies to isolate, expand and differentiate neural stem cells into the desired specific phenotypes must be developed.

Transcriptome analysis in primary neural stem cells using a tag cDNA amplification method.

Background: Neural stem cells (NSCs) can be isolated from the adult mammalian brain and expanded in culture, in the form of cellular aggregates called neurospheres. Neurospheres provide an in vitro model for studying NSC behaviour and give information on the factors and mechanisms that govern their proliferation and differentiation. They are also a promising source for cell replacement therapies of the central nervous system.

PACAP promotes neural stem cell proliferation in adult mouse brain.

In recent years, it has become evident that neural stem cells in the adult mammalian brain continuously generate new neurons, mainly in the hippocampus and olfactory bulb. Although different growth factors have been shown to stimulate neurogenesis in the adult brain, very little is known about the role of neuropeptides in this process. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with pleiotropic effects acting through three receptors to which it has high affinity, namely, PACAP receptor 1 (PAC1), vasoactive intestinal peptide (VIP) receptor 1, and VIP receptor 2.