Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND)

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD

Toward a new ‘EPOCH’: optimising treatment outcomes with phosphodiesterase type 5 inhibitors for erectile dysfunction

Despite the marked adverse impacts of erectile dysfunction (ED) on quality of life and well-being, many patients (and/or their partners) do not seek medical attention for this problem, do not receive treatment or discontinue such treatment even when it has effectively restored erectile responses to sexual stimulation. Phosphodiesterase type 5 (PDE5) inhibitors are considered first-line therapies for men with ED. To help physicians maximise the likelihood of treatment success with these agents, we conducted an English-language PubMed search of articles involving approved PDE5 inhibitors dating from 1 January 1998 (the year in which sildenafil citrate was introduced), through 31 August 2008. In addition to sildenafil, tadalafil and vardenafil, search terms included ‘adhere*’, ‘couple*’, ‘effect*’, ‘effic*’, ‘partner*’, ‘satisf*’, ‘succe*’ and ‘treatment outcome.’ Based on our analysis, physician activities to promote favourable treatment outcomes may be captured under the mnemonic ‘EPOCH’: (i) Evaluating and educating patients and partners to ensure realistic expectations of therapy; (ii) Prescribing a treatment individualised to the couple’s lifestyle needs and other preferences; (iii) Optimising treatment outcomes by scheduling follow-up visits with the patient to ‘fine-tune’ dosages and revisit key educational messages; (iv) Controlling comorbidities via lifestyle counselling, medications and/or referrals and (v) Helping patients and their partners to meet their health and psychosocial needs, potentially referring them to a specialist for other forms of therapy if they are not satisfied with PDE5 inhibitors

Evaluation of patient expectations and treatment satisfaction after 1-year tadalafil therapy for erectile dysfunction: the DETECT study.

Erectile dysfunction (ED) is a self-reported condition and satisfaction with sexual performance is individual, subjective, and multi-factorial. Treatment success depends on several outcomes. Tadalafil is a long-acting, selective inhibitor of phosphodiesterase 5 that has been shown to be effective at treating men with ED.Clinical TrialJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe