Empagliflozin in patients with autosomal dominant polycystic kidney disease (EMPA-PKD): study protocol for a randomised controlled trial.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary condition that causes the formation of cysts primarily in the kidneys. The continuous growth of multiple cysts leads to the destruction of functional parenchyma, which may progress to end-stage kidney disease. Tolvaptan is the only drug specifically approved for slowing down the progression of ADPKD.

Amino acid metabolism in kidney health and disease.

Amino acids form peptides and proteins and are therefore considered the main building blocks of life. The kidney has an important but under-appreciated role in the synthesis, degradation, filtration, reabsorption and excretion of amino acids, acting to retain useful metabolites while excreting potentially harmful and waste products from amino acid metabolism. A complex network of kidney transporters and enzymes guides these processes and moderates the competing concentrations of various metabolites and amino acid products.

Prevalence of pericardial effusion in autosomal dominant polycystic kidney disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) has numerous extrarenal manifestations. Pericardial effusion (PE) may be an underrecognized complication with a reported prevalence of up to 35%. Our study is the first to systematically evaluate the prevalence of PE and associated risk factors in an ADPKD cohort outside the USA.

The aging kidney is characterized by tubuloinflammaging, a phenotype associated with MHC-II gene expression.

Introduction: Even during physiologic aging, the kidney experiences a loss of mass and a progressive functional decline. This is clinically relevant as it leads to an increased risk of acute and chronic kidney disease. The kidney tubular system plays an important role in the underlying aging process, but the involved cellular mechanisms remain largely elusive.

Induction of ferroptosis selectively eliminates senescent tubular cells.

The accumulation of senescent cells is an important contributor to kidney aging, chronic renal disease, and poor outcome after kidney transplantation. Approaches to eliminate senescent cells with senolytic compounds have been proposed as novel strategies to improve marginal organs. While most existing senolytics induce senescent cell clearance by apoptosis, we observed that ferroptosis, an iron-catalyzed subtype of regulated necrosis, might serve as an alternative way to ablate senescent cells.

Myeloid CCR2 Promotes Atherosclerosis after AKI.

Background: The risk of cardiovascular events rises after AKI. Leukocytes promote atherosclerotic plaque growth and instability. We established a model of enhanced remote atherosclerosis after renal ischemia-reperfusion (IR) injury and investigated the underlying inflammatory mechanisms.

[What is evidence-based in the treatment of autosomal dominant polycystic kidney disease?].

The cystic transformation of the kidneys and liver are the most common symptoms of autosomal dominant polycystic kidney disease (prevalence 1:400-1:1000). A set of other manifestations can be observed less frequently, such as intracranial aneurysms. End-stage renal disease affects 50% of patients by the age of 70 years.

Induction of Stress-Induced Renal Cellular Senescence In Vitro: Impact of Mouse Strain Genetic Diversity.

Cellular senescence, a stress-induced state of irreversible cell cycle arrest, is associated with organ dysfunction and age-related disease. While immortalized cell lines bypass key pathways of senescence, important mechanisms of cellular senescence can be studied in primary cells. Primary tubular epithelial cells (PTEC) derived from mouse kidney are highly susceptible to develop cellular senescence, providing a valuable tool for studying such mechanisms.

Correction: Calcium dobesilate reduces VEGF signaling by interfering with heparan sulfate binding site and protects from vascular complications in diabetic mice.

[This corrects the article DOI: 10.1371/journal.pone.

Calcium dobesilate reduces VEGF signaling by interfering with heparan sulfate binding site and protects from vascular complications in diabetic mice.

Inhibiting vascular endothelial growth factor (VEGF) is a therapeutic option in diabetic microangiopathy. However, VEGF is needed at physiological concentrations to maintain glomerular integrity; complete VEGF blockade has deleterious effects on glomerular structure and function. Anti-VEGF therapy in diabetes raises the challenge of reducing VEGF-induced pathology without accelerating endothelial cell injury.

Claudin 19 Is Regulated by Extracellular Osmolality in Rat Kidney Inner Medullary Collecting Duct Cells.

The inner medullary collecting duct (IMCD) is subject to severe changes in ambient osmolality and must either allow water transport or be able to seal the lumen against a very high osmotic pressure. We postulate that the tight junction protein claudin-19 is expressed in IMCD and that it takes part in epithelial adaptation to changing osmolality at different functional states. Presence of claudin-19 in rat IMCD was investigated by Western blotting and immunofluorescence.

Comparison of Different Selection Strategies for Tolvaptan Eligibility among Autosomal Dominant Polycystic Kidney Disease Patients.

Background: Tolvaptan can slow down renal function decline in autosomal dominant polycystic kidney disease (-ADPKD). While there is consensus across international recommendations that the drug should only be used in patients with high risk of rapid progression, identification criteria for rapid progression vary. Here, we investigated different assessment strategies using a real-life ADPKD cohort.

Diuretic state affects ascending thin limb tight junctions.

The nephron segments in the inner medulla are part of the urine concentrating mechanism. Depending on the diuretic state, they are facing a large range of extracellular osmolality. We investigated whether water homeostasis affects tubular transport and permeability properties in inner medullary descending thin limb (IMdTL) and ascending thin limb (IMaTL).

Heterogeneity of tight junctions in the thick ascending limb.

Renal tubular transport mechanisms are optimized to be energy efficient and tailored to local gradients and transport rates. The combined transcellular action of ion channels, transporters, and pumps, together with the paracellular pathway, enables kidney function. Monogenetic diseases and mouse models indicate that both trans- and paracellular proteins can become disease-causing candidates and may be targets for future therapeutic approaches.

Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na+ and Mg2+ transport.

The thick ascending limb (TAL) of Henle's loop drives paracellular Na, Ca, and Mg reabsorption via the tight junction (TJ). The TJ is composed of claudins that consist of four transmembrane segments, two extracellular segments (ECS1 and -2), and one intracellular loop. Claudins interact within the same (cis) and opposing (trans) plasma membranes.

Corticomedullary difference in the effects of dietary Ca²⁺ on tight junction properties in thick ascending limbs of Henle's loop.

The thick ascending limb of Henle's loop (TAL) drives an important part of the reabsorption of divalent cations. This reabsorption occurs via the paracellular pathway formed by the tight junction (TJ), which in the TAL shows cation selectivity. Claudins, a family of TJ proteins, determine the permeability and selectivity of this pathway.