Does Hypertension Affect the Recovery of Renal Functions after Reversal of Unilateral Ureteric Obstruction?

Research has demonstrated that hypertension can lead to an exaggeration in the renal functional and histological changes caused by ureteral obstruction. These changes were particularly observed shortly after the release of a relatively brief period of unilateral ureteral obstruction (UUO). However, the long-term impact of hypertension on the recovery of renal functions has not been investigated beyond the immediate period after UUO reversal. In order to investigate this effect, a group of spontaneously hypertensive rats (G-SHR, n = 11) and a group of normotensive Wistar Kyoto rats (G-NTR, n = 11) were subjected to a 48 h reversible left UUO. The impact of UUO was then examined 45 days after the reversal of obstruction. The glomerular filtration rate, renal blood flow, and the fractional excretion of sodium in the post-obstructed left kidney (POK) showed similarities to the non-obstructed right kidney (NOK) in both groups. However, the changes in the albumin creatinine ratio, renal injury markers, pro-apoptotic markers, and histological changes in the G-SHR were much more pronounced compared to the G-NTR. We conclude that hypertension continues to have a significant impact on various aspects of renal injury and function, even several weeks after UUO reversal.

The Effect of Hypertension on the Recovery of Renal Dysfunction following Reversal of Unilateral Ureteral Obstruction in the Rat.

Both ureteral obstruction (UO) and hypertension are common conditions that affect kidney functions. Hypertension and chronic kidney disease are closely associated with an overlapping and intermingled cause-and-effect relationship. The effect of hypertension on the renal dysfunction following reversible UO has not been studied previously. To study this effect, spontaneously hypertensive (G-HT, n = 10) and normotensive Wistar (G-NT, n = 10) rats underwent 48-h reversible left unilateral UO (UUO), and the effect of UUO was studied 96 h following UUO reversal. The glomerular filtration rate, renal blood flow, and renal tubular functions such as the fractional excretion of sodium in the post-obstructed left kidney (POK) in both groups were significantly altered compared with the non-obstructed right kidney (NOK). However, the alterations in the G-HT were significantly more exaggerated when compared with the G-NT. Similar findings were observed with the histological features, gene expression of kidney injury markers, pro-inflammatory, pro-fibrotic and pro-apoptotic cytokines, and pro-collagen, as well as tissue levels of apoptotic markers. We conclude that hypertension has significantly exaggerated the alterations in renal functions and other parameters of renal injury associated with UUO.

Reversal Unilateral Ureteral Obstruction: A Mice Experimental Model.

BACKGROUND/AIMS: Reversible unilateral ureteral obstruction (R-UUO) is a model of renal injury used to study the structural and functional recovery of the kidneys after relief of the obstruction. This model has a prominent potential for the study of inflammatory and immune processes, cellular and tissue regeneration. Here we sought to describe a model of renal injury and repair R-UUO in mice. METHODS: Eight week-old C57BL/6J male mice were divided into 5 groups (n = 5 each): UUO day 1, 2, 3, 4 and 5. R-UUO was performed with a microvascular clamp. At day 3, the ureteral clamp was removed and nephrectomy of the contralateral kidney was performed. Mice were sacrificed 48 h afterwards (day 5). An extra group with unilateral nephrectomy without UUO was added. Wild type mice were used as controls. Blood and tissue samples were collected for creatinine, immunohistochemistry and kidney mRNA gene expression analysis. RESULTS: In the analysis of the obstructed kidney, we observed acute kidney injury with creatinine that doubled its baseline value; histological signs of tubular damage; increased inflammatory response evaluated by F4/80 macrophage; upregulation of pro-inflammatory and pro-fibrotic cytokines such as IL-2, MCP-1, CD40 and TGF-ß1 and increased α-smooth muscle actin staining and mild fibrosis. Once the clamp was removed, we observed the amelioration of the kidney function, pathological lesions and the inflammatory response. CONCLUSION: This R-UUO model is an easy, reproducible and reliable method to assess kidney recovery after obstructive uropathy. In this setting, the use of this model may help to a better understanding of the process of kidney repair.