Publications by authors named "Endlich K"

Introduction: The MiniMed™ 780G system is an advanced insulin pump system incorporating an AHCL (Advanced Hybrid Close Loop) algorithm that automatically adjusts insulin delivery based on glucose levels. All guidelines recommend the use of Automated Insulin Delivery therapy for people with type 1 diabetes (PWT1D) and they highlight that a specifically trained and expert team should provide training on HCL systems for PWT1D, but none of the publications detail the curriculum profile that diabetes educators should have. This paper aims to establish a consensus on the optimal educational pathway for diabetes educators on the MiniMed™ 780G system.

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  • The study analyzes the dynamic forces acting on podocytes during glomerular filtration, indicating that these forces are not well understood.
  • Using numerical simulations, researchers estimated shear stresses on the podocyte membrane and slit diaphragm, finding significant variations based on slit width and flow velocity.
  • The findings suggest that the filtration barrier experiences high shear and pressure stress, which can lead to podocyte detachment—a key issue in various kidney diseases.
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  • X-chromosomal genetic variants can provide important information about differences in human traits and diseases between sexes.
  • A large-scale study analyzed kidney-related traits in nearly 909,000 individuals, finding 23 genetic loci linked to uric acid levels and estimated glomerular filtration rate (eGFR), including four new genes that may play a role in kidney function.
  • The research also discovered five novel sex-specific interactions, with variations showing different effects in males and females, and highlighted genes that are responsive to androgens (male hormones), indicating a complex relationship between sex and kidney-related genetics.
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Given the increasing prevalence of chronic kidney disease (CKD) and its impact on health care, it is important to better understand the multiple factors influencing health-related quality of life (HRQOL), particularly since they have been shown to affect CKD outcomes. Determinants of HRQOL as measured by the validated Kidney Disease Quality of Life questionnaire (KDQOL) and the Patient Health Questionnaire depression screener (PHQ-9) were assessed in a routine CKD patient sample, the Greifswald Approach to Individualized Medicine (GANI_MED) renal cohort (N = 160), including a wide range of self-reported data, sociodemographic and laboratory measures. Compared to the general population, CKD patients had lower HRQOL indices.

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  • The study investigates the genetic factors contributing to the decline in estimated glomerular filtration rate (eGFR), a key indicator of kidney function, by analyzing data from 62 longitudinal studies involving over 343,000 participants.
  • Twelve significant genetic variants related to eGFR decline were identified, with most showing interaction effects based on age, which highlights how genetic influences on kidney function change as individuals get older.
  • The findings emphasize that individuals with certain genetic profiles face higher risks for kidney failure and acute kidney injury, providing valuable insights that could aid in drug development and strategies for managing kidney health.
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  • Reduced glomerular filtration rate (GFR) is a precursor to kidney failure, influenced by factors like genetics and diabetes (DM), but the interaction between these factors is not well understood.
  • A large-scale genome-wide association study (GWAS) analyzed eGFR across almost 1.5 million individuals, revealing distinct genetic loci that differ between those with and without diabetes.
  • The findings identified potential new targets for drug development aimed at protecting kidney function, highlighting that many drug interventions could be effective for both diabetic and non-diabetic populations.
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Chronic kidney disease (CKD) is a major public health burden affecting more than 500 million people worldwide. Podocytopathies are the main cause for the majority of CKD cases due to pathogenic morphological as well as molecular biological alterations of postmitotic podocytes. Podocyte de-differentiation is associated with foot process effacement subsequently leading to proteinuria.

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Background: Most patients with chronic kidney disease (CKD) are old, comorbid, and subjected to polypharmacy. This study describes prevalence and predictors of potentially inappropriate medication (PIM) in CKD patients.

Materials And Methods: Medication plans of CKD patients of the "Greifswald Approach to Individualized Medicine" cross-sectional study (GANI_MED) were checked for PIM based on kidney function (PIM-K) and PIM for elderly patients (PIM-E).

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  • * A large study investigated blood-based DNA methylation patterns in relation to kidney function and found 69 DNA sites linked to estimated glomerular filtration rate and 7 to urinary albumin-to-creatinine ratio, pointing to potential genetic markers for CKD.
  • * Further validation in kidney tissue highlighted specific genes associated with kidney function and suggested that certain DNA methylation changes could have causal effects, implicating pathways in blood cell migration and immune response related to kidney health.
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  • * The study identified 100 significant CpG sites that account for 11.6% of serum urate variance, particularly noting five CpGs associated with SLC2A9, a major gene influencing serum urate levels.
  • * Additionally, some of these CpGs also appear to mediate effects of genetic variants related to serum urate and are linked to metabolic syndrome, suggesting a potential blood DNA methylation signature for assessing cardiometabolic risk factors.
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Proper and size selective blood filtration in the kidney depends on an intact morphology of podocyte foot processes. Effacement of interdigitating podocyte foot processes in the glomeruli causes a leaky filtration barrier resulting in proteinuria followed by the development of chronic kidney diseases. Since the function of the filtration barrier is depending on a proper actin cytoskeleton, we studied the role of the important actin-binding protein palladin for podocyte morphology.

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The majority of kidney diseases arise from the loss of podocytes and from morphological changes of their highly complex foot process architecture, which inevitably leads to a reduced kidney filtration and total loss of kidney function. It could have been shown that microRNAs (miRs) play a pivotal role in the pathogenesis of podocyte-associated kidney diseases. Due to their fully functioning pronephric kidney, larval zebrafish have become a popular vertebrate model, to study kidney diseases in vivo.

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Under healthy conditions, foot processes of neighbouring podocytes are interdigitating and connected by an electron-dense slit diaphragm. Besides slit diaphragm proteins, typical adherens junction proteins are also found to be expressed at this cell-cell junction. It is therefore considered as a highly specialized type of adherens junction.

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Background/aims: Podocyte differentiation is essential for proper blood filtration in the kidney. It is well known that transcription factors play an essential role to maintain the differentiation of podocytes. The present study is focused on the basic helix-loop-helix (bHLH) transcription factor Tcf21 (Pod1) which is essential for the development of podocytes in vivo.

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Glomerular hypertension induces mechanical load to podocytes, often resulting in podocyte detachment and the development of glomerulosclerosis. Although it is well known that podocytes are mechanosensitive, the mechanosensors and mechanotransducers are still unknown. Since filamin A, an actin-binding protein, is already described to be a mechanosensor and mechanotransducer, we hypothesized that filamins could be important for the outside-in signaling as well as the actin cytoskeleton of podocytes under mechanical stress.

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Podocytes are highly specialized epithelial cells that are essential for an intact glomerular filtration barrier in the kidney. Several glomerular diseases like focal segmental glomerulosclerosis (FSGS) are initially due to podocyte injury and loss. Since causative treatments for FSGS are not available until today, drug screening is of great relevance.

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  • - The study investigates the genetic factors contributing to the rapid decline in glomerular filtration rate (eGFRcrea), using data from 42 genome-wide association studies to analyze genetic loci linked to this decline.
  • - Two specific definitions of rapid eGFRcrea decline are examined, leading to the identification of seven independent genetic variants associated with this condition, including significant findings near three novel loci.
  • - The research suggests that individuals with a higher genetic risk for kidney function decline are more likely to experience acute kidney injury, indicating that these identified genetic loci could help in developing targeted therapies and identifying at-risk individuals.
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Focal and segmental glomerulosclerosis (FSGS) is a histological pattern frequently found in patients with nephrotic syndrome that often progress to end-stage kidney disease. The initial step in development of this histologically defined entity is injury and ultimately depletion of podocytes, highly arborized interdigitating cells on the glomerular capillaries with important function for the glomerular filtration barrier. Since there are still no causal therapeutic options, animal models are needed to develop new treatment strategies.

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Hypertension is one of the central causes of kidney damage. In the past it was shown that glomerular hypertension leads to morphologic changes of podocytes and effacement and is responsible for detachment of these postmitotic cells. Because we have shown that podocytes are mechanosensitive and respond to mechanical stress by reorganization of the actin cytoskeleton , we look for mechanotransducers in podocytes.

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Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy.

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  • Increased urinary albumin-to-creatinine ratio (UACR) is linked to higher risks of kidney disease and cardiovascular issues, yet the underlying causes are not fully understood.
  • A large meta-analysis identified 68 genetic loci associated with UACR, highlighting connections to conditions like proteinuria, hyperlipidemia, and hypertension.
  • Specific genes (such as TGFB1 and PRKCI) were implicated in kidney function, and experiments showed that disrupting these genes in fruit flies affects albumin processing, suggesting new avenues for research to lower albumin levels.
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Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178).

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The solute carrier (SLC) group of membrane transport proteins includes about 400 members organized into more than 50 families. The SLC family that comprises nucleoside-sugar transporters is referred to as SLC35. One of the members of this family is SLC35F1.

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