aliskiren and Nephritis

The aim of this study was to investigate the antialbuminuric and antihypertensive effects of aliskiren by monitoring home blood pressure (BP) in comparison with the effects of the angiotensin receptor blocker (ARB) valsartan in patients with hypertensive nephrosclerosis and albuminuria.. We conducted an open-label, randomized trial to compare the effects of aliskiren with those of valsartan. Patients with BP <150/90 mmHg, an estimated glomerular filtration rate of 90-30 mL/min/1.73 m(2), and albuminuria >30 mg/g, despite treatment with a 160 mg daily dose of valsartan, were randomly assigned to the following two groups: the aliskiren group, who switched from 160 mg/day valsartan to 150 mg/day aliskiren, which was later increased to 300 mg/day (n = 20); and the valsartan group, who continued with 160 mg/day valsartan (n = 20).. After 12 weeks of treatment, although there was no significant difference in clinic BP between groups, a significant reduction in morning and evening systolic BP was observed in the aliskiren group. The decrease in albuminuria in the aliskiren group was significantly better than that in the valsartan group, and a significant correlation was noted between the change in morning systolic BP and the change in albuminuria in the aliskiren group (r = 0.564, P = 0.0084).. We showed that aliskiren treatment leads to a greater reduction in albuminuria and home systolic BP values than valsartan in patients with nephrosclerosis. We propose that aliskiren therapy should be considered as a therapeutic modality to complement ARBs in hypertensive patients with nephrosclerosis.

Topics: Adult; Aged; Albuminuria; Amides; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure Monitoring, Ambulatory; Female; Fumarates; Humans; Hypertension; Hypertension, Renal; Male; Middle Aged; Nephritis; Nephrosclerosis; Tetrazoles; Valine; Valsartan

Hypertensive nephropathy is moving up the charts to number 2 after diabetic nephropathy in terms of diagnostic frequency cited as causing end stage renal disease (ESRD).. Hypertensive nephropathy was produced in mildly hypertensive C57BL/6-(hREN)/(hAGT) double transgenic (dTG) mice with 20 mg/kg of cyclosporine A (CsA) administered subcutaneously (sc) daily for 28 days. CsA dose 20 mg/kg was selected for the study as this dose offered significant alteration in blood pressure, biochemical parameters and moderate nephropathy in kidney. Effect of aliskiren oral treatment twice daily consequently for 28 days at 10 mg/kg body weight was evaluated against CsA induced hypertensive nephropathy. Systolic blood pressure (SBP) was measured by non invasive tail cuff method. Kidney function test (blood urea nitrogen, serum creatinine, urea and uric acid) and kidney injury biomarker (tumor necrosis factor-alpha (TNF-α) and interlekin-6) level was assessed in serum, TNF-α, IL-6, transforming growth factor-beta1 (TGF-β1) and kidney injury molecule-1 (KIM-1) was assayed in kidney homogenate. Urinary KIM-1 levels were assessed as an early biomarker of nephropathy.. Significant hypertensive nephropathy and increase in serum levels of biomarkers was observed in CsA treated animals when compared with Control group. Aliskiren treatment elicited significant renoprotection by preventing the increase in blood pressure and levels of serum biomarkers and also reduced the nephropathic alterations in the kidney histoarchitecture.. A correlation between pharmacological, biochemical and histological findings has been established in mouse model. The present findings have indicated the renoprotective activity of aliskiren in CsA induced hypertensive nephropathy, which may be due to its antihypertensive, anti-inflammatory as well as anti-apoptopic action.

Topics: Amides; Animals; Blood Pressure; Cyclosporine; Cytokines; Female; Fumarates; Hypertension, Renal; Kidney; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nephritis; Renin

Renin-angiotensin system activation is involved in inflammation and fibrosis in the kidney. Aliskiren, a direct renin inhibitor, decreases renin-angiotensin system activation, including plasma renin activity and angiotensin II, but increases the prorenin level, which may promote inflammation and fibrosis in renal tissue. Thus, we evaluated whether inhibiting the renin-angiotensin system by aliskiren would decrease renal inflammation and fibrosis in a mouse model of unilateral ureteral obstruction.. Ten-week-old male C57BL/6 mice (Samtako, Kyoung Gi-Do, Korea) weighing 30 to 33 gm were divided into 4 groups, including vehicle or aliskiren treated sham operated and vehicle or aliskiren treated unilateral ureteral obstruction groups. We evaluated plasma renin activity, and plasma renin and renal mRNA expression levels of renin and (pro)renin receptor. To evaluate inflammation and fibrosis renal mRNA expression of monocyte chemotactic protein-1, osteopontin and transforming growth factor-β was measured. Hematoxylin and eosin, Masson's trichrome staining, and immunohistochemical staining for CD68, transforming growth factor-β and α-smooth muscle actin were performed.. Plasma renin activity was significantly lower in the aliskiren treated obstruction group than in the vehicle treated obstruction group. Aliskiren treatment increased renal mRNA expression of renin. The number of CD68 positive cells, and renal monocyte chemotactic protein-1 and osteopontin mRNA levels were significantly higher in mice with unilateral ureteral obstruction than in sham operated mice. Aliskiren decreased the increased levels of these inflammation markers. Aliskiren also decreased renal transforming growth factor-β mRNA expression, transforming growth factor-β and α-smooth muscle actin immunostaining, and Masson's trichrome stained areas of unilateral ureteral obstruction kidneys.. Aliskiren has anti-inflammatory and antifibrotic effects in an experimental unilateral ureteral obstruction mouse model.

Topics: Amides; Animals; Fibrosis; Fumarates; Kidney; Male; Mice; Mice, Inbred C57BL; Nephritis; Renin; Ureteral Obstruction