Reversible Unilateral Ureteral obstruction (UUO) is a common clinical problem which is caused by conditions such as urinary stones and leads to renal function alteration. There is very limited evidence from animal and clinical studies to suggest that reversible UUO affects the contralateral non-obstructed kidney. The few available animal studies addressed this effect in the immediate period post-UUO reversal. In humans, there are only some case reports which showed that UUO by urinary stone can rarely result in what is called ‘reflex anuria”. Further, the effect of reversible UUO on remote organs has not been addressed yet. Thus, the aim of this study was to investigate the long-term effect of reversible UUO on the contralateral kidney and remote organs such as the heart.

Studies were performed on Wistar rats which underwent reversible left UUO for 3 days and were sacrificed at 3, 10, 30 and 90 days post-UUO reversal for organ collection (n=10 in each group). Corresponding Sham groups underwent manipulation of the left ureter for similar periods. Rats were placed in metabolic cages for urine collection and renal functions were measured serially before and post-UUO reversal. From previous similar studies in rats, ten animals per group was sufficient demonstrate any significant differences [1, 2]

There was no difference in the serum urea, creatinine, creatinine clearance and cardiac enzymes and urinary albumin and albumin creatinine ration between the obstructed and sham groups at any point up to 90 days post-UUO.
As expected, the expression of the kidney injury markers (KIM-1 and NGAL) and pro-inflammatory cytokines such as IL-1β in the left obstructed kidney were significantly higher than the right control kidney in the obstructed groups and the left kidney in the sham operated groups at all stages post-UUO reversal. However, in the right non-obstructed kidney of the obstructed groups, these markers were found to be significantly higher than the sham groups post-reversal e.g., on 10 days post-reversal, the expression of these markers were as follows: 3.11±0.59 vs. 1.04±0.15, 1.22±0.04 vs. 0.97±0.08 and 1.73±0.21 vs. 1.02±0.10, respectively, P<0.05 for all).
In the remote organs such as the heart, the gene expressions of the inflammatory and apoptotic markers were significantly higher in the obstructed compared to sham groups e.g., at 90 days post-UUO, the expression of IL-1β, TNF-α and p53 was 1.45±0.01 vs. 1.01±0.05, 1.61±0.19 vs. 1.01±0.04 and 1.19±0.01 vs. 1.00±0.04, respectively, P<0.05 for all.

Reversible UUO for 3 days caused significant changes in the gene expression of kidney injury markers and in inflammatory and apoptotic markers of the contralateral non-obstructed kidney and other remote organs such as the heart.

Relatively short period of reversible UUO did not only affect the obstructed kidney but it also caused significant alterations in the contralateral kidney and other remote organs such as the heart. These remote effects might have clinical implications.

Hammad, F.T., et al., Despite initial recovery of GFR, long-term renal functions deteriorate following short periods of unilateral ureteral obstruction. Am J Physiol Renal Physiol, 2020. 319(3): p. F523-f533.
Hammad, F.T., A.M. Wheatley, and G. Davis, Long-term renal effects of unilateral ureteral obstruction and the role of endothelin. Kidney Int, 2000. 58(1): p. 242-50.