IntroductionTo determine the prevalence of chronic kidney disease and nephrolithiasis in people with gout, and the association between gout and prevalent or incident chronic kidney disease and nephrolithiasis.MethodsSystematic review and meta-analysis of epidemiological studies. Data sources; MEDLINE, EMBASE and CINAHL databases, hand-searched reference lists, citation history and contact with authors. Eligibility criteria: cohort, case–control or cross-sectional studies which examined the occurrence of chronic kidney disease or nephrolithiasis amongst adults with gout (with or without a non-gout comparator group) in primary care or general population samples. Prevalence and risk estimate meta-analyses were performed using a random-effects model.ResultsSeventeen studies were included in the meta-analysis (chronic kidney disease n = 7, nephrolithiasis n = 8, both n = 2). Pooled prevalence estimates of chronic kidney disease stage ≥3 and self-reported lifetime nephrolithiasis in people with gout were 24% (95% confidence interval 19% to 28%) and 14% (95% CI 12% to 17%) respectively. Gout was associated with both chronic kidney disease (pooled adjusted odds ratio 2.41, 95% confidence interval 1.86 to 3.11) and self-reported lifetime nephrolithiasis (1.77, 1.43 to 2.19).ConclusionsChronic kidney disease and nephrolithiasis are commonly found amongst patients with gout. Gout is independently associated with both chronic kidney disease and nephrolithiasis. Patients with gout should be actively screened for chronic kidney disease and its consequences.

Rationale: In pulmonary arterial hypertension (PAH), endothelial dysfunction and obliterative vascular disease are associated with DNA damage and impaired signaling of BMPR2 (bone morphogenetic protein type 2 receptor) via two downstream transcription factors, PPARγ (peroxisome proliferator-activated receptor gamma), and p53. Objective: We investigated the vasculoprotective and regenerative potential of a newly identified PPARγ-p53 transcription factor complex in the pulmonary endothelium. Methods and Results: In this study, we identified a pharmacologically inducible vasculoprotective mechanism in pulmonary arterial and lung MV (microvascular) endothelial cells in response to DNA damage and oxidant stress regulated in part by a BMPR2 dependent transcription factor complex between PPARγ and p53. Chromatin immunoprecipitation sequencing and RNA-sequencing established an inducible PPARγ-p53 mediated regenerative program regulating 19 genes involved in lung endothelial cell survival, angiogenesis and DNA repair including, EPHA2 ( ephrin type-A receptor 2 ), FHL2 ( four and a half LIM domains protein 2 ), JAG1 ( jagged 1 ), SULF2 ( extracellular sulfatase Sulf-2 ), and TIGAR ( TP53-inducible glycolysis and apoptosis regulator ). Expression of these genes was partially impaired when the PPARγ-p53 complex was pharmacologically disrupted or when BMPR2 was reduced in pulmonary artery endothelial cells (PAECs) subjected to oxidative stress. In endothelial cell-specific Bmpr2 -knockout mice unable to stabilize p53 in endothelial cells under oxidative stress, Nutlin-3 rescued endothelial p53 and PPARγ-p53 complex formation and induced target genes, such as APLN ( apelin ) and JAG1 , to regenerate pulmonary microvessels and reverse pulmonary hypertension. In PAECs from BMPR2 mutant PAH patients, pharmacological induction of p53 and PPARγ-p53 genes repaired damaged DNA utilizing genes from the nucleotide excision repair pathway without provoking PAEC apoptosis. Conclusions: We identified a novel therapeutic strategy that activates a vasculoprotective gene regulation program in PAECs downstream of dysfunctional BMPR2 to rehabilitate PAH PAECs, regenerate pulmonary microvessels, and reverse disease. Our studies pave the way for p53-based vasculoregenerative therapies for PAH by extending the therapeutic focus to PAEC dysfunction and to DNA damage associated with PAH progression.

BackgroundAn association between gout and renal disease is well-recognised but few studies have examined whether gout is a risk factor for subsequent chronic kidney disease (CKD). Additionally, the impact of urate-lowering therapy (ULT) on development of CKD in gout is unclear. The objective of this study was to quantify the risk of CKD stage ≥ 3 in people with gout and the impact of ULT.MethodsThis was a retrospective cohort study using data from the Clinical Practice Research Datalink (CPRD). Patients with incident gout were identified from general practice medical records between 1998 and 2016 and randomly matched 1:1 to patients without a diagnosis of gout based on age, gender, available follow-up time and practice. Primary outcome was development of CKD stage ≥ 3 based on estimated glomerular filtration rate (eGFR) or recorded diagnosis. Absolute rates (ARs) and adjusted hazard ratios (HRs) were calculated using Cox regression models. Risk of developing CKD was assessed among those prescribed ULT within 1 and 3 years of gout diagnosis.ResultsPatients with incident gout (n = 41,446) were matched to patients without gout. Development of CKD stage ≥ 3 was greater in the exposed group than in the unexposed group (AR 28.6 versus 15.8 per 10,000 person-years). Gout was associated with an increased risk of incident CKD (adjusted HR 1.78 95% CI 1.70 to 1.85). Those exposed to ULT had a greater risk of incident CKD, but following adjustment this was attenuated to non-significance in all analyses (except on 3-year analysis of women (adjusted HR 1.31 95% CI 1.09 to 1.59)).ConclusionsThis study has demonstrated gout to be a risk factor for incident CKD stage ≥ 3. Further research examining the mechanisms by which gout may increase risk of CKD and whether optimal use of ULT can reduce the risk or progression of CKD in gout is suggested.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1746-1) contains supplementary material, which is available to authorized users.

Summary Although we commonly work with patients with emotionally unstable personality disorder (EUPD) in community mental health teams (CMHTs), only some enter evidence-based psychological therapies. Many patients are not considered ready to engage in specialist treatments and remain in CMHTs without any clear focus or structure to their treatment, which is unsatisfactory for patients, clinicians and services. We present a fictional case and synthesise available literature and lived experience to explore readiness and ways to promote it. We highlight relevant issues for trainees to consider in practice. Patients with EUPD who have not received specialist treatment can be considered in terms of the transtheoretical model's stages of change. Identifying a patient's stage can help guide how to increase readiness for referral and decide when to refer. Interventions available to all healthcare professionals which may promote readiness include: psychoeducation, personal formulations, crisis planning, goal-setting, peer support, distress tolerance skills, motivational interviewing and mindfulness.