Ureter, the Guardian Angel of Nephron: The Impact of Pelvicalyceal System on Apoptotic Activity in an Experimental Obstructive Uropathy Model

Main Article Content

Serhat Gürocak
Volkan Ergin
Ahmet Cumaoğlu
İyimser Üre
İpek Işık Gönül
Aysel Arıcıoğlu
İbrahim Bozkırlı
Adnan Menevşe


Objective: We aimed to assess the impact of obstructive uropathy and its revision on renal apoptotic and inflammatory activity in an experimental model in rabbits.

Methods: Twenty-four rabbits were separated into four different groups. Ureteropelvic junction (UPJ) obstruction model was performed in Group 1 and 2. Ureterovesical junction (UVJ) obstruction model was performed in Group 3 and 4. Thirty days after the operations, bilateral nephrectomy was performed in Group 1 and 3. Thirty days after the initial surgery, the obstruction was revised in Group 2 and 4. Thirty days after the revision surgeries, bilateral nephrectomy was performed in Group 2 and 4. The apoptotic and inflammatory activity was measured at the protein level and nephrectomy specimens were examined histologically.

Results: Caspase 3 levels were significantly higher in operated left kidneys than the levels obtained in the right counterparts. The increase in procaspase 9 and caspase 3 activities in the UVJ obstruction group was less than those of the UPJ obstruction group (p<0.05, p<0.01, respectively). After the revision of obstruction, the decrease in procaspase 9 and caspase 3 activities was more significant in Group 4 than in Group 2 (p<0.05, p<0.01, respectively). Cyclooxygenase-2 expression decreased insignificantly in Group 2 and 4 when compared to Group 1 and 3 (p>0.05, p>0.05, respectively).

Conclusion: The rabbits with a UVJ obstruction had lower apoptotic indexes as compared to those with a UPJ obstruction. The apoptotic activity decreased to almost normal levels following an adequate revision of the obstruction in both groups, but this improvement was more significant in animals with a UVJ obstruction. 


Article Details

Original Research


Chevalier RL. Molecular and cellular pathophysiology of obstructive nephropathy. Pediatr Nephrol Berl Ger. 1999;13:612-9.

Chevalier RL. Perinatal obstructive nephropathy. Semin Perinatol. 2004;28:124-31.

Misseri R, Rink RC, Meldrum DR, Meldrum KK. Inflammatory mediators and growth factors in obstructive renal injury. J Surg Res. 2004;119:149-59.

Kluth DC, Erwig L-P, Rees AJ. Multiple facets of macrophages in renal injury. Kidney Int. 2004;66:542-57.

Gupta A, Gupta A, Nigam D, Shukla GS, Agarwal AK. Profile of reactive oxygen species generation and antioxidative mechanisms in the maturing rat kidney. J Appl Toxicol Jat. 1999;19:55-9.

Fernandez A, Kiefer J, Fosdick L, McConkey DJ. Oxygen radical production and thiol depletion are required for Ca(2+)-mediated endogenous endonuclease activation in apoptotic thymocytes. J Immunol Baltim Md 1950. 1995;155:5133-9.

Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, et al. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol. 1999;144:281-92.

Manucha W, Carrizo L, Ruete C, Vallés PG. Apoptosis induction is associated with decreased NHE1 expression in neonatal unilateral ureteric obstruction. Bju Int. 2007;100:191-8.

Nguyen HT, Bride SH, Badawy AB, Adam RM, Lin J, Orsola A, et al. Heparin-binding EGF-like growth factor is up-regulated in the obstructed kidney in a cell- and region-specific manner and acts to inhibit apoptosis. Am J Pathol. 2000;156:889-98.

Shokeir AA. Partial ureteral obstruction: a new variable and reversible canine experimental model. urology. 1995;45:953-7.

Sheerin NS, Sacks SH. Chronic interstitial damage in proteinuria. Does complement mediate tubulointerstitial injury? Kidney Blood Press Res. 1999;22:47-52.

Chevalier RL. Obstructive nephropathy: towards biomarker discovery and gene therapy. Nat Clin Pract Nephrol. 2006;2:157-68.

Schreiner GF, Harris KP, Purkerson ML, Klahr S. Immunological aspects of acute ureteral obstruction: immune cell infiltrate in the kidney. Kidney Int. 1988;34:487-93.

Sharma AK, Mauer SM, Kim Y, Michael AF. Interstitial fibrosis in obstructive nephropathy. Kidney Int.1993;44:774-88.

Vaughan ED Jr, Marion D, Poppas DP, Felsen D. Pathophysiology of unilateral ureteral obstruction: studies from Charlottesville to New York. J Urol. 2004;172(6 Pt 2):2563-9.

Miyajima A, Chen J, Lawrence C, Ledbetter S, Soslow RA, Stern J, et al. Antibody to transforming growth factor-beta ameliorates tubular apoptosis in unilateral ureteral obstruction. Kidney Int. 2000;58:2301-13.

Misseri R, Meldrum DR, Dinarello CA, Dagher P, Hile KL, Rink RC, et al. TNF-alpha mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling. Am J Physiol Renal Physiol. 2005;288:F406-11.

Hughes J, Johnson RJ. Role of Fas (CD95) in tubulointerstitial disease induced by unilateral ureteric obstruction. Am J Physiol. 1999;277(1 Pt 2):F26-32.

Choi YJ, Mendoza L, Rha SJ, Sheikh-Hamad D, Baranowska-Daca E, Nguyen V, et al. Role of p53-dependent activation of caspases in chronic obstructive uropathy: evidence from p53 null mutant mice. J Am Soc Nephrol Jasn. 2001;12:983-92.

Chung KH, Chevalier RL. Arrested development of the neonatal kidney following chronic ureteral obstruction. J Urol. 1996;155:1139-44.

Grande MT, Pérez-Barriocanal F, López-Novoa JM. Role of inflammation in túbulo-interstitial damage associated to obstructive nephropathy. J Inflamm Lond Engl. 2010;7:19.

Nørregaard R, Jensen BL, Topcu SO, Nielsen SS, Walter S, Djurhuus JC, et al. Cyclooxygenase type 2 is increased in obstructed rat and human ureter and contributes to pelvic pressure increase after obstruction. Kidney Int. 2006;70:872-81.

Kayanoki Y, Fujii J, Islam KN, Suzuki K, Kawata S, Matsuzawa Y, et al. The protective role of glutathione peroxidase in apoptosis induced by reactive oxygen species. J Biochem (Tokyo). 1996;119:817-22.

Chevalier RL, Thornhill BA, Wolstenholme JT. Renal cellular response to ureteral obstruction: role of maturation and angiotensin II. Am J Physiol. 1999;277(1 Pt 2):F41-7.

Chevalier RL, Smith CD, Wolstenholme J, Krajewski S, Reed JC. Chronic ureteral obstruction in the rat suppresses renal tubular Bcl-2 and stimulates apoptosis. Exp Nephrol. 2000;8:115-22.

Soliman SA, Shokeir AA, Mosbah A, Abol-Enein H, Barakat N, Abou-Bieh E, et al. Recoverability of renal function after relief of chronic partial unilateral ureteral obstruction: study of the effect of angiotensin receptor blocker (losartan). urology. 2010;75:848-52.

Zhou T-B, Qin Y-H, Zhou C, Lei F-Y, Zhao Y-J, Chen J, et al. Less expression of prohibitin is associated with increased caspase-3 expression and cell apoptosis in renal interstitial fibrosis rats. Nephrol Carlton Vic. 2012;17:189-96.

Harris KP, Klahr S, Schreiner G. Obstructive nephropathy: from mechanical disturbance to immune activation? Exp Nephrol. 1993;1:198-204.

Cachat F, Lange-Sperandio B, Chang AY, Kiley SC, Thornhill BA, Forbes MS, et al. Ureteral obstruction in neonatal mice elicits segment-specific tubular cell responses leading to nephron loss. Kidney Int. 2003;63:564-75.

Nguyen HT, Hsieh MH, Gaborro A, Tinloy B, Phillips C, Adam RM. JNK/SAPK and p38 SAPK-2 mediate mechanical stretch-induced apoptosis via caspase-3 and -9 in NRK-52E renal epithelial cells. Nephron Exp Nephrol. 2006;102:e49-61.