Chronic kidney disease (CKD) is known to involve inflammation, oxidative stress and apoptosis. Here, we investigated the impact of curcumin (diferuloyl methane, a phenolic turmeric pigment), which has strong antioxidant, anti-inflammatory and anti-apoptotic activities on kidney structure and function in rats with adenine-induced CKD. Rats were treated for 5 weeks with adenine to induce CKD-like renal damage and combined with three doses of curcumin. Markers of kidney function and oxidative stress were quantified in plasma, urine, renal homogenates and on kidney tissue. Curcumin was found to significantly abate adenine-induced toxic effects such as reduced creatinine clearance, elevated neutrophil gelatinase-associated lipocalin levels and raised urinary N-acetyl-b-D-glucosaminidase activities. Curcumin markedly reduced renal morphological damage and histopathological markers of inflammation, fibrosis and apoptosis. Curcumin further reduced adenine-induced hypertension, urinary albumin, the inflammatory cytokines IL-1b, IL-6 and TNF-a, cystatin C and adiponectin. It restored plasma sclerostin concentrations and lowered oxidative stress in renal homogenates. In animals treated with the two higher curcumin concentrations, alone or in combination with adenine, an increased expression of the antioxidative transcription factor Nrf2 was found as well as up-regulation of the activity of its direct target glutathione reductase, and of an indirect target, the glutathione level. In conclusion, curcumin exhibits salutary effects against adenine-induced CKD in rats by reducing inflammation and oxidative stress via up-regulation of the transcription factor Nrf2.Chronic kidney disease (CKD) is a major and growing public health problem in both developed [1] and developing countries [2]. CKD is considered a key determinant of the poor health outcome of major non-communicable diseases [3] because of the high prevalence of morbidity and mortality associated with it, mainly due to cardiovascular dysfunction. Till now, there is no drug to improve kidney function in patients with CKD. The current therapeutic approaches to slow down its progression are limited to normalization of insulin, glucose and blood pressure [4]. Therefore, the development of novel therapies to either slow or reverse the deterioration in kidney function is highly needed. In particular, interesting for this are natural products with proven safety profiles.The pathophysiological basis of CKD and its complications include inflammation, oxidative stress and apoptosis [5]. These features consistently occur in human beings and animals. They are also major mediators of the disease, exerting similar effects in chronic renal failure models in rats [6,7]. Patients and laboratory animals with CKD have high plasma concentrations of inflammatory mediators (such as C-reactive protein, tumour necrosis factor and other cytokines) and several markers of nitrosative and oxidative stress [8,9]. Turmeric (Curcuma longa) is a popular Asian spice that has been utilized for...