Soft tissue infections with S. Lugdunensis. Presentation of 2 cases and general review]

When perfusion pressure to the kidney falls, e.g., as a result of dehydration or mechanical hindrance to the renal arterial blood flow, the release of renin, hence angiotensin (Ang), surges. This feedback regulation is geared to preservation of renal hemodynamic environment by raising systemic blood pressure. We are aware that a surge of renin-angiotensin release also occurs when there is a mechanical hindrance to urine outflow. This phenomenon of ureteral pressure-sensitive activation of renin-angiotensin has been heretofore viewed as an error of nature. We have obtained evidence which challenges this traditional view when we examined strains of mutant mice which are completely devoid of either angiotensin type 1 (AT1) receptor gene (Agtr1-) or angiotensin type 2 (AT2) receptor gene (Agtr2-) as a result of genetic manipulation of these animals. These strains of mice display varying degrees of urinary tract obstruction. In Agtr2- mice obstructions develop during early kidney ontogenesis in ureto, and, in Agtr1- mice, during late ontogenesis ex utero. One may recall that, throughout its normal ontogenesis, the kidney is twice at risk for obstruction of urine outflow. Thus, in utero the ureter is transiently obliterated. This transient obliteration is believed to protect the kidney from the high pressure from the cloaca when urine is not yet formed. During this period, the ureter is surrounded by dense layers of undifferentiated mesenchymal cells. Subsequent expansive growth that the ureter must achieve, therefore, in concert with a timely disappearance of the surrounding mesenchymal cells. The study in Agtr2- embryos indicated that Ang, through the Agtr2 receptor, promotes disappearance of these mesenchymal cells, and that inactivation of this receptor results in congenital obstructive nephropathy. Our additional studies in human specimens indeed indicate that many infants with congenital anomalies of the kidney and urinary tract have a significant mutation within the AT2 gene. Once animals are born, the kidney comes to be of primary importance for preservation of body fluid homeostasis, and urinary output increases dramatically. The large volume of urine predisposes the kidney to obstructive nephropathy due to the high resistance offered to the urine by the downstream ureter. Normally, a special device develops within the urinary tract in a timely fashion, which enables the kidney to collect a bulk of urine, and then to expel it downward periodically without imposing positive pressure upon the renal parenchyma. This special device is the renal pelvis. In the studies on Agtr1 null mutant mice, we learned that Ang, through the AT1 receptor, promotes development of the pelvis shortly after birth, so that inactivation of this receptor in Agtr1- mice leads to absence of development of the pelvis, hence to obstructive nephropathy. Collectively, Agtr1 or Agtr2 null mutant mice suffer from urinary tract obstruction. Given that urinary tract obstruction per se is a potent stimulus for Ang generation, Ang is essential for the kidney to escape from obstructive injury.