2015-eb-math model rvp increase_austin-bb2
TRANSCRIPT
Aim: To inves)gate how changes in renal arterial pressure and venous pressure separately and in combina)on affect renal hemodynamic and re-‐absorp)ve func)on, in simulated states of normal, elevated and strongly elevated levels of Angiotensin II (Ang II).
Background: Heart failure (HF) is associated with impaired renal func)on. This has been aCributed to systemic hemodynamic changes: forward failure causing decreased renal arterial pressure (RAP) and backward failure causing venous conges)on and increased renal venous pressure (RVP).
Aus)n Baird1, Branko Braam2 and Anita Layton1 1 Dept. Mathema)cs, Duke Univ., Durham, NC, USA and 2 Div. Nephrology, Dept. Medicine and Dept. Physiology, Univ. of Alberta, Edmonton, AB, Canada
Conclusion: Our model implicates that a decrease in renal arterial pressure leads to a decrease in sodium excre)on under normal condi)ons, which becomes more pronounced when venous pressure is increased. Angiotensin II leads to a depression of GFR, and to a strong decrease in frac)onal sodium excre)on. Further studies will be directed to inves)gate the role of the myogenic response and tubuloglomerular feedback on renal func)on and response to changes in renal arterial and venous pressures. This research was supported in part by NIH grant DK-‐89066 and by NSF grant DMS1263995
Implica)ons of increased renal venous pressure for renal hemodynamic and reabsorp)ve func)on studied by a mathema)cal model of the kidney
IM: Inner medulla; CDs: collec)ng ducts; MD: macula densa; PCT: proximal convoluted tubule; DVR: descending vasa recta; AVR: ascending vasa recta.
RVP (mmHg)
5 10 15 20 25 30 RAP (mmHg)
80
100
120
SN
GFR
(nl
min)
0
5
10
15
20
25
30
35
5 10 15 20 25 30
RVP (mmHg)
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
Sod
ium
excr
etio
n(u
mol
/min
)
baselinelowhigh
5 10 15 20 25 30
RVP (mmHg)
50
100
150
200
250
300
350
400S
NB
F(n
l/min
)
baselinelowhigh
5 10 15 20 25 30
RVP (mmHg)
0.0
0.1
0.2
0.3
0.4
0.5
0.6
Frac
tiona
lNa
excr
etio
n(%
)
baselinelowhigh
80 100 120 140 160 180 200
RAP (mmHg)
0
2
4
6
8
10
Sod
ium
excr
etio
n(u
mol
/min
)baselinelowhigh
RVP (mmHg)
5 10 15 20 25 30 RAP (mmHg)
80
100
120
SN
GFR
(nl
min)
0
5
10
15
20
25
30
35
Inner stripe
Inner medulla
Outer stripe
Renal Venous Pressure (RVP)
Renal Arterial Pressure (RAP)
RVP (mmHg)
5 10 15 20 25 30 RAP (mmHg)
80
100
120
Frac
tiona
l Na
excr
etio
n%
0.0
0.2
0.4
0.6
0.8
1.0
1.2
Cortex
RVP (mmHg)
5 10 15 20 25 30 RAP (mmHg)
80
100
120
Frac
tiona
l Na
excr
etio
n%
0.0
0.2
0.4
0.6
0.8
1.0
1.2
RVP (mmHg)
5 10 15 20 25 30 RAP (mmHg)
80
100
120
Frac
tiona
l Na
excr
etio
n%
0.0
0.2
0.4
0.6
0.8
1.0
1.2
High Ang II
Figure 2: SNGFR and SNBF, obtained for the superficial nephron, whole kidney sodium excre)on and frac)onal sodium excre)on dependency on RVP in normal (baseline), elevated (low) and strongly (high) elevated Ang II states. RAP = 100 mmHg for all simula)ons.
RVP (mmHg)
5 10 15 20 25 30 RAP (mmHg)
80
100
120
SN
GFR
(nl
min)
0
5
10
15
20
25
30
35
Figure 3: Effects on SNGFR and frac)onal whole kidney sodium excre)on upon combined changes of RAP and RVP in normal (baseline), elevated (low) and very elevated (high) Ang II states. SNGFR reported for the superficial nephron simula)ons.
Baseline
Low Ang II
Renal Venous Pressure (RVP)
80 100 120 140 160 180 200
RAP (mmHg)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Frac
tiona
lNa
excr
etio
n(%
)
baselinelowhigh
80 100 120 140 160 180 200
RAP (mmHg)
10
20
30
40
50
60
70
SN
GF
R(n
l/min
)
baselinelowhigh
80 100 120 140 160 180 200
RAP (mmHg)
150
200
250
300
350
400
450
SN
BF
(nl/m
in)
baselinelowhigh
5 10 15 20 25 30
RVP (mmHg)
0
10
20
30
40
50
60
SN
GFR
(nl/m
in)
baselinelowhigh
References: 1. R Moss and AT Layton, AJP Renal, 2014.
Methods: We used a published and well-‐characterized mathema)cal kidney model incorpora)ng superficial and deep nephrons and renal hemodynamics, including myogenic response (MR), tubulo-‐glomerular feedback (TGF), and segmental sodium handling [1].
Figure 1: Single nephron GFR (SNGFR) blood flow (SNBF), both obtained for the superficial nephron, and whole kidney sodium excre)on and frac)onal sodium excre)on dependency on renal artery pressure (RAP) in normal (baseline), elevated (low) and strongly (high) elevated Ang II states. RVP = 5 mmHg for all simula)ons.