Image-based robotic (ROSA knee system) total knee arthroplasty with inverse kinematic alignment compared to conventional total knee arthroplasty : Study protocol and the inverse kinematic alignment in 8-steps using the ROSA Knee system for knee balancing technique explained.

Introduction: In 2020, 368 million people globally were affected by knee osteoarthritis, and prevalence is projected to increase with 74% by 2050. Relatively high rates of dissatisfactory results after total knee arthroplasty (TKA), as reported by approximately 20% of patients, may be caused by sub-optimal knee alignment and balancing. While mechanical alignment has traditionally been the goal, patient-specific alignment strategies are gaining interest.

Search for surrogate markers to predict end stage kidney disease in long term lithium users.

Background: A surrogate marker (a substitute indicator of the true outcome) is needed to predict subgroups of long-term lithium users at risk of end-stage kidney disease (ESKD). In this narrative review the aim is to determine the optimal surrogate endpoint for ESKD in long-term lithium users in a scientific context. MAIN: In a literature search in long-term lithium users, no studies on surrogate measurements on ESKD were identified.

International expert consensus statement on the diagnosis and management of congenital nephrogenic diabetes insipidus (arginine vasopressin resistance).

Congenital nephrogenic diabetes insipidus (NDI; also known as arginine vasopressin resistance) is a rare inherited disorder of water homeostasis, caused by insensitivity of the distal nephron to arginine vasopressin. Consequently, the kidney loses its ability to concentrate urine, which leads to polyuria, polydipsia and the risk of hypertonic dehydration. The diagnosis and management of NDI are very challenging and require an integrated, multidisciplinary approach.

A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.

Excessive activation of the immune system is the cause of a wide variety of renal diseases. However, the pathogenic mechanisms underlying the aberrant activation of the immune system in the kidneys often remain unknown. TRPC6, a member of the Ca-permeant family of TRPC channels, is important in glomerular epithelial cells or podocytes for the process of glomerular filtration.

[Thiazides to prevent recurrence of kidney stones: is hydrochlorothiazide still indicated?].

Thiazides are widely used to prevent recurrence of calcium-containing kidney stones. However, the recent NOSTONE trial reported no benefit of hydrochlorothiazide on the composite outcome of symptomatic or radiologic recurrence. Higher doses (25 and 50mg daily) resulted in a decrease of radiologic recurrence, but no difference in symptomatic stones.

Glycosaminoglycans and fucoidan have a protective effect on experimental glomerulonephritis.

The glomerular endothelial glycocalyx is degraded during inflammation. The glycocalyx plays a pivotal role in endothelial function and is involved in many processes including binding of chemokines and cytokines, leukocyte trafficking, and preventing proteinuria. HS-based therapeutics are a promising novel class of anti-inflammatory drugs to restore a compromised endothelial glycocalyx under inflammatory conditions.

Co-Culture of Glomerular Endothelial Cells and Podocytes in a Custom-Designed Glomerulus-on-a-Chip Model Improves the Filtration Barrier Integrity and Affects the Glomerular Cell Phenotype.

Crosstalk between glomerular endothelial cells and glomerular epithelial cells (podocytes) is increasingly becoming apparent as a crucial mechanism to maintain the integrity of the glomerular filtration barrier. However, studies directly investigating the effect of this crosstalk on the glomerular filtration barrier are scarce because of the lack of suitable experimental models. Therefore, we developed a custom-made glomerulus-on-a-chip model recapitulating the glomerular filtration barrier, in which we investigated the effects of co-culture of glomerular endothelial cells and podocytes on filtration barrier function and the phenotype of these respective cell types.

Peroxisome proliferator-activated receptor ɣ agonist mediated inhibition of heparanase expression reduces proteinuria.

Background: Proteinuria is associated with many glomerular diseases and a risk factor for the progression to renal failure. We previously showed that heparanase (HPSE) is essential for the development of proteinuria, whereas peroxisome proliferator-activated receptor ɣ (PPARɣ) agonists can ameliorate proteinuria. Since a recent study showed that PPARɣ regulates HPSE expression in liver cancer cells, we hypothesized that PPARɣ agonists exert their reno-protective effect by inhibiting glomerular HPSE expression.

Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes.

Many patients with primary focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but were never validated. We aimed to find proteins involved in the mechanism of action of CPF(s) and/or potential biomarkers for the presence of CPF(s).

Improving a Rare Metabolic Disorder Through Kidney Transplantation: A Case Report of a Patient With Lysinuric Protein Intolerance.

Lysinuric protein intolerance (LPI) is a rare metabolic disorder with reduced renal and intestinal reabsorption of ornithine, lysine, and arginine. It is due to variants in SLC7A7, the gene encoding y+L amino acid transporter 1 (y+LAT1), which lead to urea cycle defects with protein intolerance. Chronic kidney disease in lysinuric protein intolerance is common and can progress to kidney failure and initiation of kidney replacement therapy.

Novel mouse strains to study circulating permeability factor(s) in primary focal segmental glomerulosclerosis.

Recurrence of proteinuria after kidney transplantation in primary focal segmental glomerulosclerosis (FSGS) is unpredictable. Several putative circulating permeability factors (CPFs) have been suggested, but none have been validated. A clinically relevant experimental model is required that demonstrates the presence of CPF(s) in patient material, to study CPF(s) and possibly predict recurrence in patients.

Human pluripotent stem cell-derived kidney organoids for personalized congenital and idiopathic nephrotic syndrome modeling.

Nephrotic syndrome (NS) is characterized by severe proteinuria as a consequence of kidney glomerular injury due to podocyte damage. In vitro models mimicking in vivo podocyte characteristics are a prerequisite to resolve NS pathogenesis. The detailed characterization of organoid podocytes resulting from a hybrid culture protocol showed a podocyte population that resembles adult podocytes and was superior compared with 2D counterparts, based on single-cell RNA sequencing, super-resolution imaging and electron microscopy.

An update on the use of tolvaptan for autosomal dominant polycystic kidney disease: consensus statement on behalf of the ERA Working Group on Inherited Kidney Disorders, the European Rare Kidney Disease Reference Network and Polycystic Kidney Disease International.

Approval of the vasopressin V2 receptor antagonist tolvaptan-based on the landmark TEMPO 3:4 trial-marked a transformation in the management of autosomal dominant polycystic kidney disease (ADPKD). This development has advanced patient care in ADPKD from general measures to prevent progression of chronic kidney disease to targeting disease-specific mechanisms. However, considering the long-term nature of this treatment, as well as potential side effects, evidence-based approaches to initiate treatment only in patients with rapidly progressing disease are crucial.

Repurposing Riociguat to Target a Novel Paracrine Nitric Oxide-TRPC6 Pathway to Prevent Podocyte Injury.

Increased expression and activity of the Ca channel transient receptor potential channel 6 (TRPC6) is associated with focal segmental glomerulosclerosis, but therapeutic strategies to target TRPC6 are currently lacking. Nitric oxide (NO) is crucial for normal glomerular function and plays a protective role in preventing glomerular diseases. We investigated if NO prevents podocyte injury by inhibiting injurious TRPC6-mediated signaling in a soluble guanylate cyclase (sGC)-dependent manner and studied the therapeutic potential of the sGC stimulator Riociguat.

Gitelman-Like Syndrome Caused by Pathogenic Variants in mtDNA.

Background: Gitelman syndrome is the most frequent hereditary salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. Gitelman syndrome is caused by biallelic pathogenic variants in encoding the Na-Cl cotransporter (NCC) expressed in the distal convoluted tubule. Pathogenic variants of , , , or may result in the same renal phenotype of Gitelman syndrome, as they can lead to reduced NCC activity.

Laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.

Shear stress induced by laminar blood flow has a profound effect on the morphology and functional phenotype of macrovascular endothelial cells. The influence of laminar flow on the glomerular microvascular endothelium, however, remains largely elusive. The glomerular endothelium, including its glycocalyx, is a crucial part of the glomerular filtration barrier, which is involved in blood filtration.

Diagnosis and management of Bartter syndrome: executive summary of the consensus and recommendations from the European Rare Kidney Disease Reference Network Working Group for Tubular Disorders.

Bartter syndrome is a rare inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism with hypokalemic and hypochloremic metabolic alkalosis and low to normal blood pressure. The primary pathogenic mechanism is defective salt reabsorption predominantly in the thick ascending limb of the loop of Henle. There is significant variability in the clinical expression of the disease, which is genetically heterogenous with 5 different genes described to date.

Treatment and long-term outcome in primary nephrogenic diabetes insipidus.

Background: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome.

Methods: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form.

Results: Data were collected on 315 patients (22 countries, male 84%, adults 35%).

Fatigue fracture of an uncemented Zweymüller femoral stem at the neck-shoulder junction.

A fracture through the neck of the femoral stem in total hip arthroplasty is extremely rare. We report a neck fracture of a cementless Zweymüller stem, one of the most implanted stems worldwide. According to our knowledge, this is the first thorough case description of a neck fracture of a cementless Zweymüller stem.