The improvement of ischemia/reperfusion injury by erythropoetin is not mediated through bone marrow cell recruitment in rats.

BACKGROUND: Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure in kidney transplantation; however, the mechanisms of kidney damage and repair are not yet clear. So far no treatment has been effective to prevent I/R injury. In the present study we evaluated the effect of erythropoetin (EPO) in I/R injury in rats. We investigated the role of bone marrow cells (BMC) in kidney repair and the effect of EPO on BMC recruitment. MATERIALS AND METHODS: Female Sprague Dawley rats transplanted with male BMCs underwent I/R injury. In the treatment group rats received 5000 IU of EPO 30 minutes before renal ischemia. At 2 and 4 weeks after I/R, rats were humanely killed and we measured creatinine clearance (glomerular filtration rate [GFR]), proteinuria, and body weight (BW). Renal tissue was harvested for histologic and molecular analysis. Fluorescein in situ hybridization (FISH) and TUNEL were used to determined the presence of male cell chimerism and apoptosis in renal tissue. RESULTS: At 4 weeks after I/R, EPO significantly improved GFR (1.8 +/- 0.2 vs 1.2 +/- 0.14 mL/min; P < .05). No significant differences between EPO and control rats were observed in proteinuria, BW, and hemoglobin levels at 2 and 4 weeks. After death, the kidney showed only minimal tubulointerstitial changes, which were more marked in control rats. FISH analysis demonstrated a low degree of microchimerism, not significantly different between EPO and control rats. Apoptosis decreased between 2 and 4 weeks after I/R, in both EPO and control groups. CONCLUSION: EPO improved GFR and injury at 4 weeks after I/R; however, it did not enhance the recruitment of BMC.

Rapamycin reduces proteinuria and renal damage in the rat remnant kidney model.

Rapamycin is an immunosuppressive drug used to prevent acute allograft rejection in solid organ transplantation. It shows less nephrotoxicity than calcineurin inhibitors. We evaluated the effect of rapamycin in rats undergoing 5/6 nephrectomy, a model of proteinuric and progressive renal failure. Fourteen days after surgery rats were randomized either to receive rapamycin or to remain untreated (control). Rats were humanely killed on day 91; serum creatinine, creatinine clearance, and proteinuria were assessed. Renal sections were stained with periodic acid-Schiff to evaluate glomerular volume (Gv), glomerulosclerosis (GS) and tubulointerstitial damage (TIS); we evaluated GS and TIS by Sirius red staining (SR). Epithelial-to-mesenchymal transition (EMT) was assessed by immunohistochemistry. Rapamycin affected neither serum creatinine nor creatinine clearance; it reduced Gv (controls, 5.9 +/- 3.1 x 10(6); rapamycin, 1.3 +/- 0.7 x 10(6) microm(3)) and proteinuria (control, 349 +/- 146; rapamycin, 56 +/- 27 mg/24 h; P < .05); rapamycin ameliorated GS (control, 78 +/- 7; rapamycin, 36 +/- 7%; P < .05; SR: control, 13.2 +/- 3.5; rapamycin, 3.8 +/- 1.0%; P < .05), and TIS (control, 3.25 +/- 0.5; rapamycin, 1.0 +/- 0.1; P < .05; SR: control, 29 +/- 3; rapamycin, 11 +/- 3%; P < .05). Rapamycin reduced alphaSMA (control, 3.25 +/- 0.5; rapamycin, 1.0 +/- 0.1; P < .05), VIM (control, 3.5 +/- 0.6; rapamycin, 1.0 +/- 1.4; P < .05), and CD68(+) cells infiltration (control, 110 +/- 43; rapamycin, 24 +/- 1 cells; P < .05). Rapamycin slows the progression of renal damage in the rat remnant kidney and may represent a novel approach to the treatment of chronic kidney disease.