1 3 Int Urol Nephrol (2016) 48:287–297 DOI 10.1007/s11255-015-1171-1 NEPHROLOGY - ORIGINAL PAPER Effects of long-acting erythropoietin analog darbepoetin-α on adriamycin-induced chronic nephropathy Abdelaziz M. Hussein 1 · Mohamed Eldosoky 1 · Ahmed Handhle 2 · Hanaa Elserougy 1 · Mohamed Sarhan 1 · Mohamed A. Sobh 3 · Mahmoud El Hussiny 3 · Eman M. El Nashar 4 Received: 8 May 2015 / Accepted: 21 November 2015 / Published online: 10 December 2015 © Springer Science+Business Media Dordrecht 2015 Conclusion Administration of DPO-α alleviates ADR nephropathy and this might due to improvement of Hb con- tent, hyperlipidemia, enhancement of endogenous antioxi- dants, reduction of apoptosis and tubulointerstitial injury and maintaining the integrity of glomerular membrane. Keywords Darbepoetin-α · Adriamycin · Caspase-3 · Sialoproteins · Kim-1 · Electron microscope · Podocytes Introduction The prevalence of chronic kidney disease (CKD) has been growing consistently for the past decades. This alarming increase in chronic and end-stage renal disease is accompa- nied and promoted by a growing prevalence of cardiovascu- lar risk factors such as obesity, diabetes, and hypertension that increase the overall morbidity and mortality in these patients. Therefore, there is an urgent need to identify the mechanisms that perpetuate and aggravate renal dysfunc- tion and scarring, and to develop strategies to prevent and attenuate them [1]. Most types of chronic kidney disease (CKD) are characterized by the development of glomeru- losclerosis, tubulointerstitial inflammation and fibrosis [2]. Adriamycin (ADR)-induced renal failure is a well-accepted chronic disease model of progressive glomerulosclerosis in rats [3] which mirrors what seen in human CKD [2]. ADR- induced nephrosis is characterized by focal glomeruloscle- rosis [4] leading to chronic proteinuria and renal failure [5]. Reactive oxygen species (ROS) [6, 7] has been postulated to explain the underlying mechanisms of ADR-induced nephropathy; however, the exact mechanisms of ADR- induced nephrotoxicity remain poorly understood. Erythropoietin (EPO) is a glycoprotein hormone, pri- marily produced by renal cortical and outer medullary Abstract Objectives To study the effects of darbepoetin-α (DPO- α) (erythropoietin analog) on adriamycin (ADR)-induced chronic nephropathy in rats. Methods Sixty-nine male Sprague-Dawley rats divided into 3 groups (23 rats each): negative control group: normal rats received saline as a vehicle; positive control (ADR) group: rats received 2 iv injection of ADR via penile vein at 14-day interval without treatment; and DPO-α group: as ADR group but rats received sc DPO-α (0.3 μg/kg bw) once weekly for 12 weeks. By the end of experiment hemo- globin (Hb) content, serum creatinine, BUN, albumin, tri- glycerides and cholesterol, urinary protein excretion and kidney injury molecule-1 (KIM-1). GSH, malondialde- hyde, caspase-3 expression histopathological and electron microscopic examinations for kidney tissues were done. Results DPO-α significantly improved the animal sur- vival rate and body weight, Hb, serum BUN, triglycerides, cholesterol, and albumin and urinary protein excretion and KIM-1 in urine. Also, administration of DPO-α improved the morphological damage in glomeruli and renal tubules as well as caspase-3 expression and markers of oxidative stress in kidney tissues. * Abdelaziz M. Hussein zizomenna28@yahoo.com; menhag@mans.edu.eg 1 Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt 2 Medical Biochemistry Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt 3 Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt 4 Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha, Egypt