Wolfram syndrome (WFS) is a rare autosomal premature aging syndrome that shows signs of diabetes mellitus (DM), optic atrophy (OA) and deafness in addition to central nervous system and endocrine complications. The frequent form of WFS, type 1 (WFS1), harbours causative mutations in the WFS1 gene, while the rare form or type 2 (WFS2), involves CISD2. Mutations in these two genes are recognized by a subset of variable clinical symptoms and a set of overlapping features. Here we report on the generation of stable human induced pluripotent stem cells (hiPSCs) derived from primary fibroblasts of a previously reported Italian family with CISD2 mutation (c.103+1G>A), occurring in the consensus intron 1 splicing site in two sisters, deleting the first exon of the transcript. The generated hiPSCs provides a cell model system to study the mutation’s role in the multi-systemic clinical disorders previously described and test eventual drug effects on the specific and associated clinical phenotype.

There is virtually an unlimited number of possible Tissue Microarray (TMA) applications in basic and clinical research and ultimately in diagnostics. However, to assess the functional importance of novel markers, researchers very often turn to cell line model systems. The appropriate choice of a cell line is often a difficult task, but the use of cell microarray (CMA) technology enables a quick screening of several markers in cells of different origins, mimicking a genomic-scale analysis. In order to improve the morphological evaluations of the CMA slides we harvested the cells by conventional trypsinization, mechanical scraping and cells grown on coverslips. We show that mechanical scraping is a good evaluation method since keeps the real morphology very similar to those grown on coverslips. Immunofluorescence images are of higher quality, facilitating the reading of the biomarker cellular and subcellular localization. Here, we describe CMA technology in stem cell research.

Magnesium is a cofactor in cellular energy metabolism and insulin signaling, with recognized effects on vascular tone and cardiac electrophysiology. Hypomagnesemia affects roughly one-third of people with type 2 diabetes mellitus (T2DM) in pooled observational data and becomes more frequent in diabetic kidney disease (DKD). Reduced dietary intake accounts for part of the deficit; renal magnesium wasting linked to attenuated insulin signaling and reduced TRPM6 activity at the distal convoluted tubule is a plausible mechanism for the remainder, characterized mainly in cellular and experimental systems. In observational cohorts, lower serum magnesium accompanies poorer glycemic control and an excess of cardiovascular and microvascular events, and in DKD it independently predicts progression to kidney failure. Prescribed oral repletion has been associated with fewer cardiovascular events in hypomagnesemic patients, with no corresponding association in normomagnesemic ones, in propensity-matched data that cannot substitute for randomized confirmation. Mendelian randomization offers suggestive evidence for coronary artery disease and none for incident T2DM, a dissociation compatible with insulin resistance acting upstream of renal magnesium wasting, although instrument limitations leave other readings open. Hypomagnesemia is substantially less frequent in adult type 1 diabetes, where the association with glycemic control concentrates among patients with the highest insulin requirements. SGLT2 inhibitors raise serum magnesium modestly, whereas thiazide and loop diuretics and proton-pump inhibitors lower it. Randomized trials have shown modest effects on glycemic intermediates, larger in patients with documented deficiency, and no trial has yet tested renal progression. Magnesium status is a reproducible prognostic marker in T2DM and DKD; its value as a therapeutic target awaits randomized trials with clinical endpoints.

Background/Objectives: Diet is a modifiable determinant of kidney health, and sex differences in kidney physiology support sex-specific evaluation of dietary patterns. We examined the association of Planetary Health Diet Index (PHDI) adherence with cystatin C-based eGFR decline, and its modification by sex, in US adults aged 50 years and older. Methods: We analyzed 2126 Health and Retirement Study participants (950 men, 1176 women) with diet assessed by food frequency questionnaire in 2013 and cystatin C-based eGFR measured in 2012 and 2016. Survey-weighted regression models, adjusted for baseline eGFR and for demographic, socioeconomic, lifestyle and clinical covariates, related PHDI to eGFR change and to a ≥30% relative eGFR decline; sex interaction was tested on the multiplicative and additive scales. Results: PHDI adherence was nonsignificantly associated with lower eGFR decline (β per 10-point increment 0.218; 95% CI −0.065 to 0.466). Among women, each 10-point-higher score was associated with slower eGFR decline (β 0.355; 95% CI 0.029 to 0.681; p = 0.034) and 20% lower odds of ≥30% eGFR decline (OR 0.799; 95% CI 0.687 to 0.930; p = 0.005); no significant association was observed in men (β 0.080; 95% CI −0.294 to 0.454; OR 1.080; 95% CI 0.901 to 1.295). Sex modified the association with ≥30% eGFR decline on both a multiplicative (p = 0.002) and additive scale (p < 0.001). Conclusions: PHDI adherence was associated with slower kidney function decline in women aged 50 years and older, with non-significant effect in men. Sex merits consideration as a biological modifier when plant-forward diets are evaluated as potentially nephroprotective strategies.

Renal impairment affects up to half of patients with newly diagnosed multiple myeloma, and roughly 2–4% require dialysis at presentation, most often because of light-chain cast nephropathy. In these patients, renal recovery is associated with the speed and magnitude of serum free light-chain (sFLC) reduction in observational cohorts, an association that mainly reflects the hematologic response to chemotherapy; the incremental benefit of removing circulating sFLCs by extracorporeal means remains uncertain, and this narrative review is organized around that question in the current era of effective antimyeloma therapy. Plasma exchange was tested in three small randomized trials before proteasome inhibitors were available, the largest finding no benefit, and two randomized trials of high-cutoff hemodialysis on a bortezomib backbone, MYRE and EuLITE, found no benefit for their primary renal endpoints, with more pulmonary infections in the high-cutoff arm of EuLITE. Medium-cutoff membranes, polymethylmethacrylate adsorptive dialyzers, and hemodiafiltration with endogenous reinfusion have achieved substantial sFLC reduction with less albumin loss in small uncontrolled series, without any randomized comparison against conventional dialysis. Daratumumab-containing induction lowers sFLCs within days and may further narrow the residual rationale for enhanced clearance. Conventional high-flux hemodialysis combined with prompt antimyeloma therapy is therefore the evidence-based standard kidney-replacement modality when dialysis is indicated; the patient subsets in which a time-limited enhanced-removal strategy might still be tested are proposed as hypotheses for prospective trials, without validated thresholds.