Microphysiological Systems to Recapitulate the Gut–Kidney Axis

Chronic kidney disease (CKD) typically appears alongside other comorbidities, highlighting an underlying complex pathophysiology that is thought to be vastly modulated by the bidirectional gut–kidney crosstalk. By combining advances in tissue engineering, biofabrication, microfluidics, and biosensors, microphysiological systems (MPSs) have...

A Self-management Approach for Dietary Sodium Restriction in Patients With CKD: A Randomized Controlled Trial

Rationale & objective: Patients with chronic kidney disease (CKD) are particularly sensitive to dietary sodium. We evaluated a self-management approach for dietary sodium restriction in patients with CKD. Study design: Randomized controlled trial. Setting & participants: Nephrology outpatient clinics in 4 Dutch hospitals. 99 adults with CKD...

Towards human ex vivo organ perfusion models to elucidate drug pharmacokinetics in health and disease

To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions...

Discovery of early-stage biomarkers for diabetic kidney disease using ms-based metabolomics (FinnDiane study)

Diabetic kidney disease (DKD) is a devastating complication that affects an estimated third of patients with type 1 diabetes mellitus (DM). There is no cure once the disease is diagnosed, but early treatment at a sub-clinical stage can prevent or at least halt the progression. DKD is clinically diagnosed as abnormally high urinary albumin...

Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis

Renal expression of MMP-2, -9, and tissue inhibitor of MMP-1 (TIMP-1) correlates with histological disease activity in anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV). We studied whether urinary and plasma levels of MMP-2, -9, and TIMP-1 reflect renal expression of these proteins and renal disease-activity in AAV. Urine...

Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model

OBJECTIVE - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multi-system disorder characterized by progressive cyst formation in the kidneys. Serious complications of ADPKD are intracranial and aortic aneurysms. The condition is mainly caused by mutations in the PKD1 or PKD2 gene. We have carefully analyzed vascular remodeling in...

Henoch-Schönlein purpura in children: An epidemiological study among Dutch paediatricians on incidence and diagnostic criteria

Background: The aim of the present study on the occurrence of Henoch-Schönlein Purpura (HSP) in Dutch children is to give some insight into the epidemiology of HSP in the Netherlands, to record the diagnostic criteria used by Dutch paediatricians and to evaluate the accuracy of the latter using the presence of IgA in the skin when biopsies are...

Health issues of whey proteins: 1. Protection of lean body mass

Loss of muscle mass as a consequence of changes in protein metabolism during periods of catabolic stress is a serious complication in a variety of conditions. These conditions are weight loss programs, sarcopenia in the elderly and several clinical states. It appears from many studies that improved protein nutrition by ingestion of high-quality...

A thirteen week dietary toxicity study with 7-hydroxymatairesinol potassium acetate (HMRlignan) in rats

Plant lignan 7-hydroxymatairesinol (7-HMR) is a novel precursor of the mammalian lignan enterolactone. A 13 week toxicity study at dietary levels of 0, 0.25, 1, and 4% (w/w) of potassium acetate complex of 7-HMR (HMRlignan) was conducted in the Wistar rat. These dietary levels resulted in an average daily intake of 160, 640, and 2600 mg...

Randvoorwaarden aan een verblijf op grote hoogte bij bestaande gezondheidsproblemen [Preconditions for a stay in high altitude areas in the case of existing health problems]

Various symptoms can arise during a stay in high altitude areas (above 2500 m), such as tissue hypoxia and in particular pulmonary and brain oedema. Patients with existing health problems can expect to develop more complaints or more severe complaints at an earlier stage. For a number of these patients a stay in high altitude areas should be...

Toxicology of chemical mixtures: Challenges for today and the future

A major challenge for the toxicologist involved in safety evaluation of chemical mixtures is to test the hypothesis that as a rule exposure to mixtures of chemicals at (low) non-toxic doses of the individual chemicals is of no health concern. A series of repeated dose studies in rats with defined mixtures of chemicals with the same or different...

Subacute (4-wk) oral toxicity of a combination of four nephrotoxins in rats: Comparison with the toxicity of the individual compounds

In a 4-wk study, 10-wk-old Wistar rats were fed the nephrotoxins hexachloro-1,3-butadiene (HCBD), mercuric chloride, d-limonene and lysinoalanine either alone or in combination. These nephrotoxins damage epithelial cells of the proximal tubules, but by different mechanisms. Each chemical was given alone at a Minimum-Nephrotoxic-Effect Level ...

Chronic (89-week) feeding study with hydroxypropyl distarch phosphate, starch acetate, lactose and sodium alginate in mice