The association of tamoxifen with losartan and mycophenolate mofetil significantly reduced albuminuria (3 vs 130 mg/24h) and promoted additional antifibrotic effects in a rat model of hypertensive nephrosclerosis.
Does the addition of tamoxifen to losartan and mycophenolate mofetil improve renal fibrosis, inflammation, and renal function in a rat model of hypertensive nephrosclerosis?
The addition of tamoxifen to standard conservative therapy (losartan and mycophenolate mofetil) provides synergistic antifibrotic and anti-inflammatory effects in experimental hypertensive nephrosclerosis.
Absolute Event Rate: 3% vs 130%
p-value: p=<0.05
CKD progression depends on the activation of an intricate set of hemodynamic and inflammatory mechanisms, promoting renal leukocyte infiltration, inflammation and fibrosis, leading to renal function loss. There are currently no specific drugs to detain renal fibrogenesis, which is a common end-point for different nephropathies. Clinical therapy for CKD is mostly based on the management of hypertension and proteinuria, partially achieved with renin-angiotensin-aldosterone system (RAAS) blockers, and the control of inflammation by immunosuppressive drugs. The aim of the present study was to verify if the administration of tamoxifen (TAM), an estrogen receptor modulator, clinically employed in the treatment of breast cancer and predicted to exert antifibrotic effects, would promote additional benefits when associated to a currently used therapeutic scheme for the conservative management of experimental CKD. Wistar rats underwent the NAME model of hypertensive nephrosclerosis, obtained by daily oral administration of a nitric oxide synthesis inhibitor, associated to dietary sodium overload. The therapeutic association of TAM to losartan (LOS), and mofetil mycophenolate (MMF) effectively reduced the severe hypertension, marked albuminuria and glomerular damage exhibited by NAME animals. Moreover, the association also succeeded in limiting renal inflammation in this model, and promoted further reduction of ECM interstitial accumulation and renal fibrosis, compared to the monotherapies. According to our results, the association of TAM to the currently used conservative treatment of CKD added significant antifibrotic effects both in vivo and in vitro, and may represent an alternative to slow the progression of chronic nephropathy.
Fanelli et al. (Sat,) conducted a other in Hypertensive nephrosclerosis (Chronic Kidney Disease) (n=65). Tamoxifen (TAM) + Losartan (LOS) + Mycophenolate Mofetil (MMF) vs. Untreated NAME model (L-NAME + high sodium diet) was evaluated on Urinary albumin excretion rate (UAE) in mg/24h (p=<0.05). The association of tamoxifen with losartan and mycophenolate mofetil significantly reduced albuminuria (3 vs 130 mg/24h) and promoted additional antifibrotic effects in a rat model of hypertensive nephrosclerosis.