ANALYSIS OF RENAL DYSFUNCTION’S PROGNOSTIC VALIDITY IN CHRONIC HEART FAILURE
L. Khorunzha, O. Titarenko, A. Merzon
National Medical University, Donetsk, Ukraine
Purpose
to analyze the value of renal dysfunction in patients with chronic heart failure
The curves of the frequency distribution
of the glomerular activity in CG (dotted line) and CHF
class IV (solid line)
(CHF) as the independent predictor of adverse outcomes.
The curve of the average glomerular activity in the
patients with CHF shows a decrease of 22 percent
in comparison with the CG. Nephrons loss in CHF
is highly improbable. But the majority of its cortical
nephrons (a big segment of the curve) arein the
conditions of pronounced ischemia, which results
in a decreased glomerular activity. Blood flow to
justamedullary nephrons (a small segment of the
curve) remains nearly or entirely normal, as well
as their glomerular activity.
Methods
We’ve retrospectively analyzed renal hemodynamics and functions in 385 patients
with CHF various severity consecutive admitted in our clinic (92.5% with rheumatic
heart disease, 87.6% 18-50 years old, 72.3% women). The control group (CG)
included 76 health voluntaries (90.3% 20-50 years old, 59.4% women). Were studied
the clearances (C) of diodrast (D), creatinin (Cr) and exogenous lithium (Li), maximal
tubular transport of D and glucose (G), glucose titration curves (TCg) and renal Na and
water excretion. Renal vein catheterization was performed in 4 persons of CG and in 7
pts with CHF NYHA IV.
Maximal rate of proximal transport functions –
diodrast secretion (TmD)
and glucose reabsorbtion (TmG)
Results
Renal hemodynamics
Renal vein catheterization
D clearance, ml/min
700
CG
D extraction ratio
A O2 - V O2 vol%
0, 92
TmD, mg/min
4
NYHA Class II CHF
0, 91
0, 91
NYHA Class III CHF
600
NYHA Class IV CHF
0, 9
3, 5
3, 41
CD/TmD
TmG, mg/min
12
60
CD/TmG
2
400
670,3
500
1,8
3
* - p<0,01 vs CG
350
0, 88
10
50
1,6
2, 5
40
*- p<0,05
0, 86
51,2
0, 85
1, 76
0, 84
1,88
6
1, 35
200
8,4
298,7
1
268,3
1,27
7,6
39,6
242,4
1, 16
200
1,2
310,1
42,3
30
1, 5
0, 84
0,8
18
0,18
16
0,16
99,8
Distal RNa
Proximal RNa
CNa/CLi, %%
10
CLi/CCr, %%
30
9
99,6
25
0,193
8
14
99,4
0,14
7
12
20
0,171
99,2
0,12
6
10
0,1
28,6
99
16,4
8
0,08
13,94
4
98,8
99,02
6
10
3
2
98,81
0,025
* *
2
0
* *
*
98,4
10,9
3,4
98,77
4
0,04
27,3
5,9
98,6
0
15
99,67
0,06
0,02
9,1
13,22
7,94
0,1
5
*
*
98,2
1
*
*
0
5
*
0
* - p<0,05
Sodium excretion is reliably lower in the initial stage of CHF. In process of the
occurrence and increase of oedema sodium excretion is drastically reduced to the
minimum. A decrease in natriuresis in patients with CHF is determined by two
mechanisms: by a significant reduction of filtered load of sodium on the one hand and
by an ever increasing reabsorption on the other. In NYHA III it increases only in distal
nephron (CNa/CLi decrease on 3.2%, p<0.05), in NYHA IV proximal tubular
reabsorption also increases (CLi/Ccr decrease on 17.7%, p <0.01), with distal delivery
of tubular fluid falling. This intrarenal shift and nonosmotic hypervasopressinemia
disturb renal hydruretic function causing water retention.
Mechanisms of decreasing natriuresis function
in CHF - correlation analysis
20
4
Na tubular R
1,13
150
1
0,2
Na reabsorption
%%
Na filtration
load
250
12
390,6
Na filtration load
mM/min
1,4
361,7
8
2
300
Na excretion
mM/min
300
57
400
Renal sodium transport
0,95
5,4
0,6
0, 82
212,7
0, 5
100
*
0
*
*
R+0,679←p<0,001→R -0,874
100
0,4
10
p>0,05
0, 8
*
p<0,02
2
*
*
*
*
*
50
*
*
0,2
0
CG
Class IV
CG
Class IV
Diodrast extraction ratio confirms that CD is an accurate measure to define the
volume of plasma flow filtered through functioning nephrons (primarily cortical ones)
in all groups of the examined. Hence, even in patients with severe CHF no detectable
number of non-functioning nephrons can be found in kidneys despite pronounced
ischemia, and their morphologically intact parenchymal cells reduce severity of
hypoxia due to the increasing oxygen uptake from the blood supplying the kidneys.
Glucose titration curves (GTC) in CG (A)
and in patients with CHF NYHA class IV (B)
0
0
0
*
*
0
A maximal rate of tubular secretion of diodrast (TmD) and a maximal rate of tubular
reabsorption of glucose (TmG) in patients with CHF are found to be 20-32 % lower
possibly due to marked ischemic parenchymal changes. The lack of blood flow to
cortical nephrons is manifested more significantly than the impairment of transport
activities of proximal tubular epithelium Relatively intact functions can be likely attributed
to the increasing oxygen uptake from the blood perfusing the renal tubules (CD).
Glomerular filtration rate
Ccr, ml/min
BUN, mg/dl
20
120
* - p<0,05
Blood pH
7,48
18
7,48
7,46
100
* - p<0,05
16
17,6
20
12
In CHF cases the glomerular
activity is evenly decreased, so
that the sequence of glucose
saturation for tubular epithelium
in different types of nephrons
remains unchanged. That’s why,
a form of the curve for glucose
transport (GTC) remains the
same as in the CG. Therefore,
kidneys
in
CHF
are
as
homogenous in terms of their
functions as normal.
7,42
113,5
60
16,9
10
95,3
7,43
14
94,3
7,4
8
56,5
40
6
20
*
*
*
7,38
7,4
7,39
4
*
*
7,36
2
0
The decrease in natriuresis in patients with CHF has a close correlative cause-andeffect relationship with both pathogenetic mechanisms: a positive correlation is
observed between the decrease in natriuresis and the reduction in filtered load of
sodium, and a negative correlation is found between the decrease in natriuresis and
the increase in sodium tubular reabsorption. The decrease of natriuresis is in a more
closed correlative connection (and hence, a casual dependence) with an increasing
sodium tubular reabsorption than with the reduction in its filtered load (differences
between correlation ratio is statistically reliable, p<0,001).
Conclusions
7,44
14
80
Na excretion
0
7,34
Creatinine clearance as indicated of the total volume of glomerular filtrate
becomes distinctly reduced in process of the deterioration of CHF. In group NYHA
cl. IV it is below the normal value twofold. Can we regard it as cardio-renal
failure? Though BUN levels demonstrate an average increase on 26-48%, we
haven’t discovered other evidences of renal failure. Moreover, instead of
pronounced acidosis which is characteristic of uraemia, patients with severe CHF
develop metabolic alkalosis attributed to the increased excretion of acids.
1. The cardiac kidney is morphologically intact, the number of functioning
nephrons remains normal even in severe cases of CHF.
2. Even in early stages of CHF activation of neurohumoral and hormonal axes
results in an impairment in renal hemodynamics and transport functions transforming
homeostatic negative feedback into positive one. A vicious circle occurs where
progressive renal sodium and water retention cause and aggravates oedematous
disorders, which by-turn determine clinical course and outcome.
3. Renal dysfunction is an important pathogenic factor of forming and progression
of CHF. It includes many components, therefore defined prognostic information in big
populations can be obtained even with some rates of different renal processes (for
example, GFR, R Na, R H2O).