Background: The high frequency of outpatient visits after kidney transplantation is burdensome to both the recovering patient and health care capacity. Self-monitoring kidney function offers a promising strategy to reduce the number of these outpatient visits. Objective: The objective of this study was to investigate whether it is safe to rely on patients’ self-measurements of creatinine and blood pressure, using data from a self-management randomized controlled trial. Methods: For self-monitoring creatinine, each participant received a StatSensor Xpress-i Creatinine Meter and related test material. For self-monitoring blood pressure, each participant received a Microlife WatchBP Home, an oscillometric device for blood pressure self-measurement on the upper arm. Both devices had a memory function and the option to download stored values to a computer. During the first year post transplantation, 54 patients registered their self-measured creatinine values in a Web-based Self-Management Support System (SMSS) which provided automatic feedback on the registered values (eg, seek contact with hospital). Values registered in the SMSS were compared with those logged automatically in the creatinine device to study reliability of registered data. Adherence to measurement frequency was determined by comparing the number of requested with the number of performed measurements. To study adherence to provided feedback, SMSS-logged feedback and information from the electronic hospital files were analyzed. Results: Level of adherence was highest during months 2-4 post transplantation with over 90% (42/47) of patients performing at least 75% of the requested measurements. Overall, 87.00% (3448/3963) of all registered creatinine values were entered correctly, although values were often registered several days later. If (the number of) measured and registered values deviated, the mean of registered creatinine values was significantly lower than what was measured, suggesting active selection of lower creatinine values. Adherence to SMSS feedback ranged from 53% (14/24) to 85% (33/39), depending on the specific feedback. Conclusions: Patients’ tendency to postpone registration and to select lower creatinine values for registration and the suboptimal adherence to the feedback provided by the SMSS might challenge safety. This should be well considered when designing self-monitoring care systems, for example by ensuring that self-measured data are transferred automatically to an SMSS.@en

Accumulating evidence demonstrates important roles for metabolism in cell fate determination. However, it is a challenge to assess metabolism at a spatial resolution that acknowledges both heterogeneity and cellular dynamics in its tissue microenvironment. Using a multi-omics platform to study cell-type-specific dynamics in metabolism in complex tissues, we describe the metabolic trajectories during nephrogenesis in the developing human kidney. Exploiting in situ analysis of isotopic labeling, a shift from glycolysis toward fatty acid β-oxidation was observed during the differentiation from the renal vesicle toward the S-shaped body and the proximal tubules. In addition, we show that hiPSC-derived kidney organoids are characterized by a metabolic immature phenotype that fails to use mitochondrial long-chain fatty acids for energy metabolism. Furthermore, supplementation of butyrate enhances tubular epithelial differentiation and maturation in cultured kidney organoids. Our findings highlight the relevance of understanding metabolic trajectories to efficiently guide stem cell differentiation.@en

The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet cells. Using drug-induced ER stress and cytoskeleton modification models, we demonstrate that altering the islet structure triggers an unfolding protein response that causes the downregulation of β-cell maturity genes. Collectively, our findings illus-trate the close relationship between endoplasmic reticulum homeostasis and β-cell phenotype, and strengthen the concept of altered β-cell identity as a mechanism underlying the loss of functional β-cell mass.@en

In chronic kidney disease (CKD), endothelial injury, is associated with disease progression and an increased risk for cardiovascular complications. Circulating cells with vascular reparative functions are hematopoietic and also reduced in CKD. To explore the mechanistic basis behind these observations, we have investigated hematopoietic stem cell (HSC) homeostasis in a mouse model for non-progressive CKD-mineral and bone disorder with experimentally induced chronic renal failure (CRF). In mice subjected to 12 weeks of CRF, bone marrow HSC frequencies were decreased and transplantation of bone marrow cells from CRF donors showed a decrease in long-term HSC repopulation compared to controls. This loss was directly associated with a CRF-induced defect in the HSC niche affecting the cell cycle status of HSC and could not be restored by the PTH-reducing agent cinacalcet. In CRF, frequencies of quiescent (G0) HSC were decreased coinciding with an increase in hematopoietic progenitor cells (HPC) in the S-and G2-phases of cell cycle. Moreover, in CRF mice, HSC-niche supporting macrophages were decreased compared to controls concomitant to impaired B lymphopoiesis. Our data point to a permanent loss of HSC and may provide insight into the root cause of the loss of homeostatic potential in CKD.@en