Rosiglitazone treatment attenuates expression of inflammatory hallmarks in the remaining kidney following contralateral nephrectomy.
OBJECTIVE
Following kidney donation, living kidney donors have been reported to develop anemia and pronounced inflammation. Therapeutic strategies for ameliorating unilateral nephrectomy-induced inflammation would be beneficiary for the living donors. We applied rosiglitazone to attenuate inflammatory processes ongoing within the remaining kidney following contralateral nephrectomy.


METHODS
20 Sprague-Dawley rats were subjected to left unilateral nephrectomy and 20 others to sham operation. Half of each group was treated for 2 weeks with rosiglitazone (5 mg/kg body weight). After sacrifice, intrarenal transforming growth factor (TGF)-beta, angiotensin-II (A-II), interleukin (IL)-6, IL-10, IL-4 and nitric oxide (NO) were assessed, and histologic sections stained to assess the inflammatory cell infiltration. Renal function was evaluated by creatinine, urea, cystatin C measurements.


RESULTS
Intrarenal IL-6, A-II and TGF-beta were significantly augmented, while NO was significantly decreased in kidneys remaining after contralateral nephrectomy. Rosiglitazone treatment abrogated augmented IL-6, A-II and TGF-beta synthesis and restored intrarenal NO availability in the remaining kidneys. Rosiglitazone also augmented anti-inflammatory IL-4 cytokine synthesis, while IL-10 production, leukocyte infiltration and renal function parameters remained unchanged.


CONCLUSIONS
Rosiglitazone treatment attenuates the proinflammatory responses, represented by augmented IL-6, A-II and TGF-beta production, developing in the remaining kidney following contralateral nephrectomy. In addition, by stimulating IL-4 synthesis and restoring NO availability, rosiglitazone treatment initiates counteractive anti-inflammatory responses in the remaining kidney.
Efrati
Shai
S
Nephrology Division, Assaf Harofeh Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Zerifin, Israel. efratishai@013.net
Berman
Sylvia
S
Chachashvili
Avraham
A
Cohen
Natan
N
Averbukh
Zhan
Z
Weissgarten
Joshua
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001795:Blood Pressure Determination; D016207:Cytokines / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D007668:Kidney; D016030:Kidney Transplantation / Q000379:methods*; D019520:Living Donors; D008297:Male; D009392:Nephrectomy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone