On slip of a viscous fluid through proximal renal tubule with linear reabsorption

<p>The hydrodynamical problem of flow in proximal renal tubule is investigated. Axisymmetric flow of viscous, incompressible fluid through the proximal renal tubule that undergoes linear reabsorption with slip at the wall is considered. The stream function is used to transform the governing equations to system of ordinary differential equations. The analytical solutions for velocity components, pressure distribution, fractional reabsorption and the shear stress are found. The effect of slip parameter and reabsorption rate on the flow have been investigated. The points of extreme values for the axial and radial velocity components are identified. The solution is applied to physiological data from human and rat kidney, and the results are presented in tables and graphs.</p>

Impact of SGLT Inhibitors on Multiple Organ Defects in Diabetes

Introduction: Diabetes leads to multiple organ defects and cellular dysfunctions such as increased expression of sodium-glucose like transporters (SGLTs). These transporters contribute to glucose homeostasis through glucose reabsorption in the proximal renal tubule. When inhibited, it results in reduced hyperglycemia, increased glucosuria and decreased HbA1c. Aims: This review article summarizes the positive and adverse effects of the three main SGLT inhibitors used in Europe, on different organs with the aim of providing useful information to clinicians in order to select the adapted SGLT inhibitor in regard to patient health problems. Discussion: Recently, SGLT pharmacological inhibitors have been developed to manage hyperglycemia in diabetic patients. SGLT inhibitors like canagliflozin, dapagliflozin, empagliflozin were approved by the Food and Drug Administration (FDA) in 2013 for use in Europe. Beyond their impact on glucose re-uptake by the kidney, these inhibitors exert beneficial pleiotropic effects. Nevertheless, several studies have recently warned the scientific community regarding adverse effects of these agents. Therefore, clinicians should consider these effects to adapt the treatment regarding patients’ health. Conclusion: The use of SGLT inhibitor in the treatment of type 2 diabetes should be considered with the perspective of general health state of the patient. In fact, SGLT inhibitors promote pleiotropic effects, among which some are beneficial for certain organs while some are deleterious.

Combinatorial expression of claudins in the proximal renal tubule and its functional consequences

The proximal renal tubule (PT) is characterized by a highly conductive paracellular pathway, which contributes to a significant amount of solute and water reabsorption by the kidney. Claudins are tight junction proteins that, in part, determine the paracellular permeability of epithelia. In the present study, we determined the expression pattern of the major PT claudins. We found that claudin-2 and claudin-10 are coexpressed throughout the PT, whereas claudin-3 is coexpressed with claudin-2 predominantly in the proximal straight tubule. Additionally, claudin-2 and claudin-3 are expressed separately within mutually exclusive populations of descending thin limbs. We developed a novel double-inducible Madin-Darby canine kidney I cell model to characterize in vitro the functional effect of coexpression of PT claudins. In keeping with previous studies, we found that claudin-2 alone primarily increased cation (Na+ and Ca2+) permeability, whereas claudin-10a alone increased anion (Cl−) permeability. Coexpression of claudin-2 and claudin-10a together led to a weak physical interaction between the isoforms and the formation of a monolayer with high conductance but neutral charge selectivity. Claudin-3 expression had a negligible effect on all measures of cell permeability, whether expressed alone or together with claudin-2. In cells coexpressing a claudin-2 mutant, S68C, together with claudin-10a, inhibition of cation permeability through the claudin-2 pore with a thiol-reactive pore blocker did not block anion permeation through claudin-10a. We conclude that claudin-2 and claudin-10a form independent paracellular cation- and anion-selective channels that function in parallel.