Inhibition of renin activity slows down the progression of HIV-associated nephropathy.
In the present study, we evaluated the effect of inhibition of renin activity (aliskiren) on the progression of renal lesions in two different mouse models (Vpr and Tg26) of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN). In protocol A, Vpr mice were fed either water (C-VprA) or doxycycline [Doxy (D-VprA)] in their drinking water for 6 wk. In protocols B and C, Vpr mice received either normal saline (C-VprB/C), Doxy + normal saline (D-VprB/C), or Doxy + aliskiren (AD-VprB/C) for 6 wk (protocol B) or 12 wk (protocol C). In protocols D and E, Vpr mice were fed Doxy for 6 wk followed by kidney biopsy. Subsequently, half of the mice were administered either normal saline (D-VprD/E) or aliskiren (AD-VprD/E) for 4 wk (protocol D) or 8 (protocol E) wk. All D-VprA mice showed renal lesions in the form of focal segmental glomerular sclerosis and dilatation of tubules. In protocols B and C, aliskiren diminished both progression of renal lesions and proteinuria. In protocol C, aliskiren also diminished (P < 0.01) the rise in blood urea. In all groups, Doxy-treated mice displayed increased serum ANG I levels (the product of plasma renin activity); on the other hand, all aliskiren-treated mice displayed diminished serum ANG I levels. Renal tissues of D-VprC displayed increased ANG II content; however, aliskiren attenuated renal tissue ANG II production in AD-VprC. In protocol D, AD-VprD showed a 24.2% increase in the number of sclerosed glomeruli compared with 139.2% increase in sclerosed glomeruli in D-VprD (P < 0.01) from their baseline. The attenuating effect of aliskiren on the progression of renal lesions continued in AD-VprE. Aliskiren also diminished blood pressure, proteinuria, and progression of renal lesions in Tg26 mice. These findings indicate that inhibition of renin activity has a potential to slow down the progression of HIVAN.
Division of Kidney Diseases and Hypertension, North Shore Long Island Jewish Medical Center, New Hyde Park, NY, USA.
Dileep
D
Kumar
Andrei
A
Plagov
Iti
I
Yadav
Deepti D
DD
Torri
Swapna
S
Sayeneni
Ankita
A
Sagar
Partab
P
Rai
Madhuri
M
Adabala
Rivka
R
Lederman
Nirupama
N
Chandel
Guohua
G
Ding
Ashwani
A
Malhotra
Pravin C
PC
Singhal
D016263:AIDS-Associated Nephropathy / Q000188:drug therapy* / Q000473:pathology; D000577:Amides / Q000627:therapeutic use; D000818:Animals; D001706:Biopsy; D018450:Disease Progression; D004318:Doxycycline / Q000008:administration & dosage; D005650:Fumarates / Q000627:therapeutic use; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D007668:Kidney / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D012084:Renin-Angiotensin System / Q000502:physiology; D000092502:Renin Inhibitors
D000577:Amides; D004318:Doxycycline; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren