More Than Bone Health: The Many Roles for Vitamin D

Vitamin D is well known for its important roles in maintaining calcium homeostasis and bone mineralization via the regulation of calcium mobilization and renal reabsorption, and the intestinal absorption of both calcium and phosphorus [...]

The effects of zinc deficiency on homeostasis of twelve minerals and trace elements in the serum, feces, urine and liver of rats

Background Zinc deficiency can change the concentrations of minerals and trace elements in the body. However, previous studies still had many limitations. Objective To reveal the effects of zinc deficiency on homeostasis of 16 minerals and trace elements. Methods Forty-five rats were divided randomly into three groups: normal zinc diet (30 mg/kg), low zinc diet (10 mg/kg), and pair-fed diet(30 mg/kg). The concentrations of 16 minerals and trace elements in serum, feces, urine, and liver were measured by inductively coupled plasma mass spectrometry. The excretion of 16 elements in urine and feces were calculated and compared. Results Zinc-deficient rats exhibited significant changes in up to 12 minerals and trace elements. The low zinc diet induced decreased excretion of zinc and concentrations of zinc in serum, feces, urine, and liver. Zinc deficiency increased feces concentrations of Mg, Cu, Se, K, Ag, Fe and Mn; decreased the concentrations of Mg, Cu, Se, K in liver and urine, and a diminished amount of Ag was observed in serum. Decreased urinary concentrations of Zn Ca, Mg, Cu, Se, K, Na, As and Cr, suggested that zinc-deficient rats increased the 9 elements’ renal reabsorption. Decreased concentrations of Ca in liver, urine, and feces, decreased excretion in urine and feces and increased serum total Ca suggested that zinc deficiency increased the redistribution of Ca in serum or other tissues. Zinc deficiency increased excretion of Cu, Se, Fe; and decreased the excretion of other 8 elements except for Ag. Conclusions Zinc deficiency changed the excretion, reabsorption and redistribution of 12 minerals and trace elements in rats. Our findings are the first to show that zinc deficiency alters the concentrations of Ag, Cr, and As. Graphical abstract

Renal Reabsorption of Folates: Pharmacological and Toxicological Snapshots

Folates are water-soluble B9 vitamins that serve as one-carbon donors in the de novo synthesis of thymidylate and purines, and in the conversion of homocysteine to methionine. Due to their key roles in nucleic acid synthesis and in DNA methylation, inhibiting the folate pathway is still one of the most efficient approaches for the treatment of several tumors. Methotrexate and pemetrexed are the most prescribed antifolates and are mainly used in the treatment of acute myeloid leukemia, osteosarcoma, and lung cancers. Normal levels of folates in the blood are maintained not only by proper dietary intake and intestinal absorption, but also by an efficient renal reabsorption that seems to be primarily mediated by the glycosylphosphatidylinositol- (GPI) anchored protein folate receptor α (FRα), which is highly expressed at the brush-border membrane of proximal tubule cells. Folate deficiency due to malnutrition, impaired intestinal absorption or increased urinary elimination is associated with severe hematological and neurological deficits. This review describes the role of the kidneys in folate homeostasis, the molecular basis of folate handling by the kidneys, and the use of high dose folic acid as a model of acute kidney injury. Finally, we provide an overview on the development of folate-based compounds and their possible therapeutic potential and toxicological ramifications.

Renal reabsorption in 3D vascularized proximal tubule models

Three-dimensional renal tissues that emulate the cellular composition, geometry, and function of native kidney tissue would enable fundamental studies of filtration and reabsorption. Here, we have created 3D vascularized proximal tubule models composed of adjacent conduits that are lined with confluent epithelium and endothelium, embedded in a permeable ECM, and independently addressed using a closed-loop perfusion system to investigate renal reabsorption. Our 3D kidney tissue allows for coculture of proximal tubule epithelium and vascular endothelium that exhibits active reabsorption via tubular–vascular exchange of solutes akin to native kidney tissue. Using this model, both albumin uptake and glucose reabsorption are quantified as a function of time. Epithelium–endothelium cross-talk is further studied by exposing proximal tubule cells to hyperglycemic conditions and monitoring endothelial cell dysfunction. This diseased state can be rescued by administering a glucose transport inhibitor. Our 3D kidney tissue provides a platform for in vitro studies of kidney function, disease modeling, and pharmacology.

Saving the sweetness: renal glucose handling in health and disease

Glucose homeostasis is highly controlled, and the function of the kidney plays an integral role in this process. The exquisite control of blood glucose relies, in part, on renal glucose filtration, renal glucose reabsorption, and renal gluconeogenesis. Particularly critical to maintaining glucose homeostasis is the renal reabsorption of glucose; with ~162 g of glucose filtered by the kidney per day, it is imperative that the kidney have the ability to efficiently reabsorb nearly 100% of this glucose back in the bloodstream. In this review, we focus on this central process, highlighting the renal transporters and regulators involved in both the physiology and pathophysiology of glucose reabsorption.