The kidneys play a fundamental role in the long-term control of arterial pressure by regulating sodium balance and extracellular fluid volume. The renin-angiotensin system (RAS) is at the center of the regulation of hypertension and progressive renal injury. It has gradually become clear that not only systemic RAS, but also intrarenal RAS has specific effects in the pathogenesis and progression of hypertension and renal damage. All of the RAS components are exhibited in the kidney and intrarenal angiotensin II (Ang II) is formed by multiple mechanisms. The demonstration of much enhanced levels of Ang II within specific renal compartments points out selective local regulation of Ang II in the kidney, showing that intrarenal Ang II levels are regulated in a way different from circulating Ang II. The importance of the RAS in involving proper nephrogenesis is also well known, and suppression of the RAS during fetal development may play a key role in mediating the structural and physiological changes observed in models of fetal programming of hypertension.

ABSTRACT:We investigated whether genetic polymorphisms of vascular endothelial growth factor (VEGF) and transforming growth factor-␤1 (TGF-␤1), potential candidate genes in the pathogenesis of urinary tract infection (UTI) and vesicoureteral reflux (VUR), are associated with the susceptibility to UTI and VUR, and renal scarring. We recruited 89 controls and 86 UTI and 58 VUR children. The UTI group was subdivided into two groups according to renal scarring. Two polymorphisms of VEGF and three of TGF-␤1 genes were investigated by using PCR-restriction fragment length polymorphism analysis. In both UTI and VUR groups, there was an increase in frequency of the VEGF -460 CC (control, 4.3; UTI, 15.9; VUR, 17.8%; p Ͻ 0.05), TGF-␤1 -509 CC (control, 8.7; UTI, 34.6; VUR, 35.1%; p Ͻ 0.001), and TGF-␤1 -800 GG genotypes (control, 19.1; UTI, 40.5; VUR, 40.4%; p Ͻ 0.05). An increase in the TGF-␤1 ϩ869 CC (scar-positive, 35.4; scar-negative, 10.3%; p Ͻ 0.05) and a decrease in the ϩ869 TC genotype (scar-positive, 29.2; scarnegative, 55.2%; p Ͻ 0.05) were observed in the scar-positive subjects. There were no differences in ϩ405 VEGF genotype frequencies. The VEGF T-460C and the TGF-␤1 C-509T, G-800A, and T869C polymorphisms could be genetic markers of the process of UTI and VUR. (Pediatr Res 62: 183-187, 2007)

Our results suggest that uNGAL, uKIM-1 and sCysC levels may be useful for predicting and managing febrile UTIs in children.

Renal disease is a worldwide health issue. Besides transplantation, current therapies revolve around dialysis, which only delays disease progression but cannot replace other renal functions, such as synthesizing erythropoietin. To address these limitations, cell‐based approaches have been proposed to restore damaged kidneys as an alternative to current therapies. Recent studies have shown that stem cell‐derived secretomes can enhance tissue regeneration. However, many growth factors undergo rapid degradation when they are injected into the body in a soluble form. Efficient delivery and controlled release of secreting factors at the sites of injury would improve the efficacy in tissue regeneration. Herein, we developed a gel‐based delivery system for controlled delivery of trophic factors in the conditioned medium (CM) secreted from human placental stem cells (HPSCs) and evaluated the effect of trophic factors on renal regeneration. CM treatment significantly enhanced cell proliferation and survival in vitro. Platelet‐rich plasma (PRP) was used as a delivery vehicle for CM. Analysis of the release kinetics demonstrated that CM delivery through the PRP gel resulted in a controlled release of the factors both in vitro and in vivo. In an acute kidney injury model in rats, functional and structural analysis showed that CM delivery using the PRP gel system into the injured kidney minimized renal tissue damage, leading to a more rapid functional recovery when compared with saline, CM, or vehicle only injection groups. These results suggest that controlled delivery of HPSC‐derived trophic factors may provide efficient repair of renal tissue injury. stem cells translational medicine 2019;8:959&970