The effect of darbepoetin alfa on renal fibrosis in rats with acute unilateral ureteral obstruction.

OBJECTIVES: The most important treatment strategy for obstructive nephropathy is to protect renal tissue from the deleterious effects of fibrosis. Therefore, we sought to investigate the renoprotective effects of darbepoetin alfa on unilateral ureteral obstructions.

METHODS: We used 12 female and 12 male 3-monthold Wistar rats weighing between 250 and 350 g. The rats were divided equally into sham, darbepoetin and control groups. With the exception of the sham group, left unilateral obstructions were applied to all of the rats. The darbepoetin group received perioperative darbepoetin alfa at a dose of 10 mg/kg. The rats were sacrificed on postoperative day 7, and 3-cc blood samples and bilateral renal specimens were collected from each rat.

RESULTS: Renal ectasia was observed significantly less frequently in the darbepoetin group than the obstruction group (p<0.001). Additionally, the uptake rates of cortical TNF and medullary SMA in the darbepoetin group were comparable to those in the sham group but lower than those in the ureteral obstruction group (p<0.001 and p<0.008, respectively). When biomarkers of renal injury, including cystatin-C, malondialdehyde, and B2 microglobulin, were evaluated in combination, B2 microglobulin was found at higher levels in the ureteral obstruction group (p<0.004).

CONCLUSION: As we know pelvicalyceal ectasia reflects intrapelvic pressure into renal tubular system via renal reflux. Therefore pelvicalyceal ectasia can be used as an indicator of renal tubular pressure. Although as a limitation of our study, renal tubular pressure was not quantitatively evaluated, parallelism between levels of renal ectasia detected in the rats of the sham, and DPO groups can predict that this drug (darbepoetin-a) can decrease renal tubular pressure in acute ureteral obstruction. Moreover, B2 microglobulin levels in the sham, and DPO groups differed from those of ureteral obstruction group, which suggested that DPO does not impair renal perfusion in addition to its decreasing effects on renal tubular pressure. We think that in countries with higher incidence rates of stone disease similar to our country, DPO may be used among medical treatment alternatives, which aim to preserve renal reserve.