Patient stories about their dialysis experience biases others' choices regardless of doctor's advice: an experimental study.

BACKGROUND: Renal services provide resources to support patients in making informed choices about their dialysis modality. Many encourage new patients to talk with those already experiencing dialysis. It is unclear if these stories help or hinder patients' decisions, and few studies have been conducted into their effects. We present two studies comparing the impact of patient and doctor stories on hypothetical dialysis modality choices among an experimental population. METHODS: In total, 1694 participants viewed online information about haemodialysis and continuous cycling peritoneal dialysis and completed a questionnaire. In Study 1, using actors, treatment information was varied by presenter (Doctor, Patient), order of presenter (Patient first, Doctor first) and mode of delivery (written, video). Information in Study 2 was varied (using actors) by presenter (Doctor, Patient), order of presenter (Patient first, Doctor first), inclusion of a decision table (no table, before story, after story) and sex of the 'patient' (male, female) and 'Doctor' (male, female). Information was controlled to ensure comparable content and comprehensibility. RESULTS: In both studies, participants were more likely to choose the dialysis modality presented by the patient rather than that presented by the doctor. There was no effect for mode of delivery (video versus written) or inclusion of a decision table. CONCLUSIONS: As 'new' patients were making choices based on past patient experience of those already on dialysis, we recommend caution to services using patient stories about dialysis to support those new to the dialysis in delivering support to those who are new to the decision making process for dialysis modality.

Upregulation of Hic-5 in glomerulosclerosis and its regulation of mesangial cell apoptosis.

Glomerulosclerosis is characterized by the loss of glomerular cells by apoptosis and deposition of collagen type I into the normal collagen IV-containing mesangial matrix. We sought to determine the alterations that might contribute to these changes by performing proteomic analysis of rat mesangial cell lysates comparing cells cultured on normal collagen type IV to those grown on abnormal collagen type I surfaces. Subculture on collagen type I was associated with changed expression of several proteins, including a significant upregulation of the paxillin-like LIM protein, hydrogen-peroxide-induced clone 5 (Hic-5), and increased the susceptibility of the cells to apoptosis in response to physiological triggers. When we knocked down Hic-5 (using siRNA), we found mesangial cells grown on collagen type I were protected from apoptosis to the same degree as untreated cells grown on collagen type IV. Further we found that the level of Hic-5 in vivo was almost undetectable in control rats but increased dramatically in the glomerular mesangium of remnant kidneys 90 and 120 days after subtotal nephrectomy. This induction of Hic-5 paralleled the upregulation of mesangial collagen type I expression and glomerular cell apoptosis. Our results suggest that Hic-5 is pivotal in mediating the response of mesangial cells to attachment on abnormal extracellular matrix during glomerular scarring.

Expression of alpha-actinin-4 in acquired human nephrotic syndrome: a quantitative immunoelectron microscopy study.

BACKGROUND: The molecular basis for the alteration of glomerular podocyte phenotype in nephrotic syndrome probably involves adaptive changes of the actin cytoskeleton. alpha-Actinin-4 is an actin cross-linking protein that also interacts with intra- and intercellular adhesion molecules and elements of the transmembrane signal transduction pathway and is implicated in nephrotic syndrome by animal models and human genetic studies. METHODS: We have performed the first quantitative immunoelectron microscopy study of alpha-actinin-4 expression in humans, analysing 12 cases of minimal change nephrosis (MCNS) and 16 cases of idiopathic membranous nephropathy (MGN), and comparing this with expression in normal tissue from seven nephrectomies (Nx). alpha-Actinin-4 was visualized by immunogold labelling of plastic-embedded whole glomerular cross-sections, and analysed using LUCIA software. RESULTS: Despite podocyte effacement, alpha-actinin-4 expression (group mean+/-1 SD) in MCNS was similar to that seen in normal Nx podocytes. In contrast, alpha-actinin-4 expression in MGN was significantly higher than in MCNS or Nx (P<0.001). Furthermore, in MGN cases showing a segmental deposition, expression of alpha-actinin-4 was significantly higher only in those capillary loop segments containing deposits, whereas in those segments without deposits expression was unchanged compared with that seen in Nx (P<0.001). alpha-Actinin-4 expression was higher in MGN cases where subepithelial deposits abutted podocyte cytoplasm, and lower in disease stages where deposits were contained within the glomerular basement membrane or were being reabsorbed. CONCLUSIONS: Elevated alpha-actinin-4 expression is observed only in MGN, and only in areas of subepithelial deposits. Further investigation into the cause of this may reveal insights into the pathogenesis of acquired nephrosis.

Post-embedding double-labeling of antigen-retrieved ultrathin sections using a silver enhancement-controlled sequential immunogold (SECSI) technique.

In electron microscopy, the post-embedding immunogold technique provides a high degree of resolution and the possibility of quantitation owing to the intrinsic characteristics of the colloidal gold marker. Application of this technique to the subcellular localization of multiple antigens by differential labeling using gold markers of different sizes, or to double labeling using the same primary antibody isotype with serial silver enhancement, has been reported. We have incorporated this double labeling technique into a modified procedure that produces excellent labeling and ultrastructural preservation, even after exposure of ultrathin sections large enough to cover a 300- micro m-diameter single-hole grid to hot antigen retrieval solutions and prolonged labeling protocols.