Sex-specific Effects of SGLT2 Inhibition in a Kidney with Reduced Nephron Number: Modeling and Analysis

The kidney plays an essential role in regulating the homeostasis of electrolytes, acid-base species, and fluids. Kidney structure and function are significantly affected in diabetes. These pathophysiological changes include glomerular hyperfiltration and tubular hypertrophy, and ultimately leading to diabetic kidney disease. A class of medications that have shown promise in slowing the progression to diabetic kidney disease are the sodium-glucose cotransporter 2 (SGLT2) inhibitors. SGLT2 inhibitors target Na+ and glucose reabsorption along the proximal convoluted tubule, enhance urinary glucose, Na+ and fluid excretion, and lower hyperglycemia in diabetes. We postulate that both diabetes-induced and SGLT2 inhibition-induced changes in kidney may exhibit significant sex differences, because the distribution of renal transporters along the nephron may be markedly different between women and men, as recently shown in rodents. The goals of this study are to (i) analyze how kidney function is altered in male and female patients with diabetes, (ii) assess the renal effects, in women and men, of an anti-hyperglycemic therapy that inhibits the sodium-glucose cotransporter 2 (SGLT2) in the proximal convoluted tubules, and (iii) study how those renal effects are altered in uninephrectomy. To accomplish these goals, we have developed computational models of kidney function, separate for male and female patients with diabetes and/or uninephredctomy. The simulation results indicate that by inducing osmotic diuresis in the proximal tubules, SGLT2 inhibition reduces paracellular transport, eventually leading to diuresis and natriuresis.

The Therapeuticrole of Moringa Oleifera Against Bisphenol A toxicity That Induce Renal Effects in Rats

The objective of the current work was to induce histological lesions by BPA(Bisphenol A)and then diagnosis the therapeutic role of Moringa oleifera. 66 adult male rats were used in the present work and divided as following: Rats were administrated (orally) normal saline as control group. Rats group were administrated (orally) 5mg BPA and divided into 4 subgroups were each subgroup treated with Moringa oleifera (100mg/kg, 200mg/kg, 300mg/kg and 400mg/kg), respectively. Rats were administrated (orally) 10mg BPA and divided to 4 subgroups were each subgroup treated with Moringa oleifera (100mg/kg, 200mg/kg, 300mg/kg and 400mg/kg), respectively. The findings of BPA groups showed significant (P<0.05) elevated in urea and creatinine with different histological lesions in the kidney include damaged glomerulus, degeneration of tubules cells, and lymphocytes infiltration. After treatment with Moringa oleifera, renal parameters and kidney tissues were back to the normal state and non-significant (P≤0.05) changes compared with the control group.