Ethical Considerations for the Inclusion of Patient-Reported Outcomes in Clinical Research: The PRO Ethics Guidelines.

Importance: Patient-reported outcomes (PROs) can inform health care decisions, regulatory decisions, and health care policy. They also can be used for audit/benchmarking and monitoring symptoms to provide timely care tailored to individual needs. However, several ethical issues have been raised in relation to PRO use.

Ethics review of COVID-19 human challenge studies: A joint HRA/WHO workshop.

This report of a joint World Health Organization (WHO) and United Kingdom (UK) Health Research Authority (HRA) workshop discusses the ethics review of the first COVID-19 human challenge studies, undertaken in the midst of the pandemic. It reviews the early efforts of international and national institutions to define the ethical standards required for COVID-19 human challenge studies and create the frameworks to ensure rigorous and timely review of these studies. This report evaluates the utility of the WHO's international guidance document Key criteria for the ethical acceptability of COVID-19 human challenge studies (WHO Key Criteria) as a practical resource for the ethics review of COVID-19 human challenge studies.

Further evidence for the association of MMP9 with nephropathy in type 2 diabetes and application of DNA pooling technology to candidate gene screening.

Background: Diabetic nephropathy is characterised by extracellular matrix (ECM) expansion, a key modulator of which is TGF-b1. Glucose-stimulated transcriptional activation of the TGF-b1 gene is an important component of the pathogenesis of nephropathy, following which latent TGF-b1 protein is synthesised. Matrix metalloproteinase 9 (MMP9) remodels the ECM and has been implicated in TGF-b1 activation.

Diabetic nephropathy, inflammation, hyaluronan and interstitial fibrosis.

Hyaluronan (HA) is a ubiquitous connective tissue glycosaminoglycan component of most extracellular matrices and alterations in its synthesis have been suggested to be involved in the glomerular changes of diabetic nephropathy. Similarly it has been suggested that macrophages are involved in the initiation of diabetic glomerular injury. Much less is known regarding the role of the prognostic value of changes in interstitial HA and interstitial inflammatory infiltrate.

Myeloma renal disease: presentation and outcome.

Background: Renal disease can be the first presentation of multiple myeloma (MM) or develop during the disease process.

Aim: To define the mode of presentation of MM to nephrologists and determine the association with patient characteristics and outcome.

Methods: MM patients referred to a tertiary renal unit were studied retrospectively.

Sp1 and Sp3 mediate constitutive transcription of the human hyaluronan synthase 2 gene.

The linear glycosaminoglycan hyaluronan (HA) is synthesized at the plasma membrane by the HA synthase (HAS) enzymes HAS1, -2, and -3 and performs multiple functions as part of the vertebrate extracellular matrix. Up-regulation of HA synthesis in the renal corticointerstitium, and the resultant extracellular matrix expansion, is a common feature of renal fibrosis. However, the regulation of expression of these HAS isoforms at transcriptional and translational levels is poorly understood.

The impact of an out-reach clinic on referral of patients with renal impairment.

Background: Early diagnosis and prompt treatment of a number of renal diseases may delay renal failure, obviate the need for renal replacement therapy and reduce co-morbidity. The aim of this study was to examine the impact of out-reach renal clinics on patterns of referral of patients with renal impairment to a nephrologist.

Methods: The number of patients with renal impairment was determined as defined by serum creatinine levels >150 micromol/l in three centres within a single NHS trust over two separate 1-week periods.

Peritoneal dialysis training: a multisensory approach.

Undertaking peritoneal dialysis (PD) therapy poses a challenge to all patients with renal failure. The potentially high risk of infection makes it essential that patients undertaking PD have adequate training and ongoing support. Over recent years, increasing numbers of elderly patients, patients with significant learning disabilities, and patients with marked comorbidities have been accepted onto renal replacement therapy programs.

Anemia and diabetes in the absence of nephropathy.

Objective: Patients with diabetes commonly have a greater degree of anemia for their level of renal impairment than those presenting with other causes of renal failure. To clarify the contribution and differing roles of diabetes and nephropathy in the development of anemia in diabetic patients, we examined the hematologic and hematinic parameters of diabetic patients without nephropathy.

Research Design And Methods: The study group was comprised of 62 patients with type 2 diabetes who had been followed for a median of 7 years.

The Euro-Balance Trial: the effect of a new biocompatible peritoneal dialysis fluid (balance) on the peritoneal membrane.

Background: Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy (RRT), concerns remain regarding the bioincompatible nature of standard PD fluid. In order to evaluate whether a newly formulated fluid of neutral pH, and containing low levels of glucose degradation products (GDP), resulted in improved in vivo biocompatibility, it was compared in a clinical study to a standard PD fluid.

Methods: In a multicenter, open, randomized, prospective study with a crossover design and parallel arms, a conventional, acidic, lactate-buffered fluid (SPDF) was compared with a pH neutral, lactate-buffered, low GDP fluid (balance).

Identification and analysis of the promoter region of the human hyaluronan synthase 2 gene.

Hyaluronan (HA) is a linear glycosaminoglycan of the vertebrate extracellular matrix that is synthesized at the plasma membrane by the HA synthase (HAS) enzymes HAS1, -2 and -3. The regulation of HA synthesis has been implicated in a variety of extracellular matrix-mediated and pathological processes, including renal fibrosis. We have recently described the genomic structures of each of the human HAS genes.

Identification and management of diabetic nephropathy in the diabetes clinic.

Objective: To examine the prevalence and management of diabetic nephropathy in a diabetes clinic.

Research Design And Methods: Characteristics of nephropaths identified by existing screening practice (phase I, albuminuria >20 mg/l in three separate urine samples), were compared with those identified by a nurse-led management program (phase II, in which screening for nephropathy was based on albumin-to-creatinine ratio in a single random urine specimen).

Results: In phase I, 644 patients attended a diabetes clinic over a 6-month period.

Peritoneal dialysis: changes to the structure of the peritoneal membrane and potential for biocompatible solutions.

Background: Peritoneal dialysis (PD) is now established as a viable and successful alternative to hemodialysis (HD) for patients starting on renal replacement therapy. A number of studies have confirmed that equivalent adequacy and fluid balance are provided at least for the first four to five years of renal replacement therapy (RRT). Loss of peritoneal membrane function remains a major factor leading to treatment failure in a significant number of patients on PD.

Morphologic changes in the peritoneal membrane of patients with renal disease.

This study examined the morphologic features of the parietal peritoneal membranes of 130 patients undergoing peritoneal dialysis (PD) and compared them with the features of the peritoneal membranes of normal individuals, uremic predialysis patients, and patients undergoing hemodialysis. The median thickness of the submesothelial compact collagenous zone was 50 microm for normal subjects, 140 microm for uremic patients, 150 microm for patients undergoing hemodialysis, and 270 microm for patients undergoing PD (P < 0.001 for all versus normal subjects).