Mean sojourn time, overdiagnosis, and reduction in advanced stage prostate cancer due to screening with PSA: implications of sojourn time on screening

This study aimed to assess the mean sojourn time (MST) of prostate cancer, to estimate the probability of overdiagnosis, and to predict the potential reduction in advanced stage disease due to screening with PSA. The MST of prostate cancer was derived from detection rates at PSA prevalence testing in 43 842 men, aged 50–69 years, as part of the ProtecT study, from the incidence of non-screen-detected cases obtained from the English population-based cancer registry database, and from PSA sensitivity obtained from the medical literature. The relative reduction in advanced stage disease was derived from the expected and observed incidences of advanced stage prostate cancer. The age-specific MST for men aged 50–59 and 60–69 years were 11.3 and 12.6 years, respectively. Overdiagnosis estimates increased with age; 10–31% of the PSA-detected cases were estimated to be overdiagnosed. An interscreening interval of 2 years was predicted to result in 37 and 63% reduction in advanced stage disease in men 65–69 and 50–54 years, respectively. If the overdiagnosed cases were excluded, the estimated reductions were 9 and 54%, respectively. Thus, the benefit of screening in reducing advanced stage disease is limited by overdiagnosis, which is greater in older men

Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD): study protocol for establishing a core outcome set in polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life threatening inherited kidney disease and is responsible for 5-10% of cases of end-stage kidney disease (ESKD). Cystic kidneys may enlarge up to 20 times the weight of a normal kidney due to the growth of renal cysts, and patients with ADPKD have an increased risk of morbidity, premature mortality, and other life-time complications including renal and hepatic cyst and urinary tract infection, intracranial aneurysm, diverticulosis, and kidney pain which impair quality of life. Despite some therapeutic advances and the growing number of clinical trials in ADPKD, the outcomes that are relevant to patients and clinicians, such as symptoms and quality of life, are infrequently and inconsistently reported. This potentially limits the contribution of trials to inform evidence-based decision-making. The Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) project aims to establish a consensus-based set of core outcomes for trials in PKD (with an initial focus on ADPKD but inclusive of all stages) that patients and health professionals identify as critically important. METHODS: The five phases of SONG-PKD are: a systematic review to identify outcomes that have been reported in existing PKD trials; focus groups with nominal group technique with patients and caregivers to identify, rank, and describe reasons for their choices; qualitative stakeholder interviews with health professionals to elicit individual values and perspectives on outcomes for trials involving patients with PKD; an international three-round Delphi survey with all stakeholder groups (including patients, caregivers, healthcare providers, policy makers, researchers, and industry) to gain consensus on critically important core outcome domains; and a consensus workshop to review and establish a set of core outcome domains and measures for trials in PKD. DISCUSSION: The SONG-PKD core outcome set is aimed at improving the consistency and completeness of outcome reporting across ADPKD trials, leading to improvements in the reliability and relevance of trial-based evidence to inform decisions about treatment and ultimately improve the care and outcomes for people with ADPKD

Medullary sponge kidney: state of the art

Medullary sponge kidney (MSK) is a kidney malformation that generally manifests with nephrocalcinosis and recurrent renal stones; other signs may be renal acidification and concentration defects, and pre-calyceal duct ectasias. MSK is generally considered a sporadic disorder, but an apparently autosomal dominant inheritance has also been observed. As MSK reveals abnormalities in both the lower and the upper nephron and is often associated with urinary tract developmental anomalies, its pathogenesis should probably be sought in one of the numerous steps characterizing renal morphogenesis. Given the key role of the GDNF-RET interaction in kidney and urinary tract development and nephrogenesis, anomalies in these molecules are reasonable candidates for explaining a disorder such as MSK. As a matter of fact, we detected two, hitherto unknown, rare variants of the GDNF gene in MSK patients. We surmise that a defective distal acidification has a central role in MSK and is followed by a chain of events including defective bone mineralization, hypercalciuria, hypocitraturia and stone formation