sodium-bromide and Kidney-Diseases

A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown. In this study, we administered daily for 16 weeks 75 mg/kg or 250 mg/kg (within clinical dosage) NaBr or NaCl (control) via drinking water to 6-week-old AS mice (mouse model of X-linked AS). Treatment with 75 mg/kg NaBr had no effect on AS progression. Surprisingly, compared with 250 mg/kg NaCl, 250 mg/kg NaBr exacerbated the progressive proteinuria and increased the serum creatinine and blood urea nitrogen in AS mice. Histological analysis revealed that glomerular injury, renal inflammation and fibrosis were exacerbated in mice treated with 250 mg/kg NaBr compared with NaCl. The expressions of renal injury markers (Lcn2, Lysozyme), matrix metalloproteinase (Mmp-12), pro-inflammatory cytokines (Il-6, Il-8, Tnf-α, Il-1β) and pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) were also exacerbated by 250 mg/kg NaBr treatment. Notably, the exacerbating effects of Br- were not observed in wild-type mice. These findings suggest that Br- supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM diseases such as AS.

Topics: Animals; Blood Urea Nitrogen; Bromides; Creatinine; Disease Models, Animal; Glomerular Basement Membrane; Kidney; Kidney Diseases; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Nephritis; Nephritis, Hereditary; Nitrogen; Potassium Compounds; Proteinuria; Sodium Compounds

Protein-energy malnutrition is seen in patients with advanced stages of chronic kidney disease (CKD) and is even more pronounced in patients receiving long-term hemodialysis treatment. Both entities have great impact on patient morbidity and mortality. Analysis of body composition is an integral part of nutritional assessment and includes the estimation of muscle, fat, and fat-free mass, as well as the extracellular water compartment. Clinical assessment of these compartments is difficult, and gold-standard methods such as tracer dilution, magnetic resonance imaging, and dual-energy x-ray absorptiometry are expensive, cumbersome, and rarely available. We report an ongoing study of body composition in hemodialysis patients involving deuterium and sodium bromide dilution, total body potassium counting, magnetic resonance imaging, whole-body and segmental bioimpedance spectroscopy, and anthropometry. The goals of the study are (1) to validate bioimpedance technology against gold-standard methods for assessment of the various body compartments, (2) to directly quantify visceral adipose tissue mass, a potential source of cytokine production (adipokines) promoting chronic inflammation, and to study its relation to inflammatory markers, and (3) to directly quantify visceral organ mass and to study its relation to uremia toxin generation as assessed by protein catabolic rate and resting energy expenditure. Preliminary results based on up to 40 hemodialysis patients are reported.

Topics: Adipose Tissue; Adult; Aged; Anthropometry; Body Composition; Body Mass Index; Body Water; Bromides; Deuterium; Electric Impedance; Female; Humans; Indicator Dilution Techniques; Inflammation; Intra-Abdominal Fat; Kidney Diseases; Magnetic Resonance Imaging; Male; Middle Aged; Muscle, Skeletal; Potassium Radioisotopes; Protein-Energy Malnutrition; Renal Dialysis; Sodium Compounds; Uremia