Q.337.What is the importance of B.P. control in the renoprotection strategy?
RENOPROTECTION
Revise please the abbreviation list on:
https://draft.blogger.com/u/0/blog/post/edit/8610857019469578230/4564412989605988372
Q.337.What is the importance of B.P. control in the renoprotection
strategy?
A. “Hypertensive Nephrosclerosis” is the 2nd most common cause of ESRD, superseded only by D.M..
So, anti-H.T. measures are the cornerstone of reno-protection. Low B.P. 8 favorable prognosis in
Dc.s & non-Dc.s. C
Q.338. When could the B.P. control be of a maximum benefit?
A. According
to “Madrid Study”, “Baseline
proteinuria”8is
the most potent determinant of
B.P. control benefit, with greatest renoprotection of the lowered B.P. goal occ. in
ptn. é higherFbasal proteinuria. In type II. D.M., reduction
of Fsystolic B.P., may be relevant.
Q.339. Mention
some of the studies concerned é role of B.P. control & proteinuria in
renoprotection?
A.“A.A.S.K.”study: African American Study
of Kidney Disease & H.T. study: Effect of B.P. lowering &
anti.-H.T. in dis. progression. 2002.:8 Similar
B.P. lowering, but more renoprotection é FRamipril comp. to Amlodepine in
proteinuric H.T. blacks.
“R.E.I.N.”study : B.P. control for Renoprotection In Non-Dcs
é CRF. Lancet 2005.
“M.D.R.I.D.”
study: Modification of Diet in Renal Disease. Ann
Int Med 1995.,8 Maximum
benefit of B.P. lowering é higher proteinuria.
Q.340. What
are the recommended targets for systolic, diastolic B.P.
& its relation to the level of proteinuria?
A. A
recommendation of (120-130)
systolic & (80-85) mmhg
diastolic,
for microalbuminuricis is widely accepted.
Moreover, systolic B.P. is more closely related to Reno/
Cardioprotection . As regard the level
of proteinuria:
< one g. 8 flat relation between B.P. lowering & renal risk.
> one g. 8 Reduction of systolic B.P. (110-129) mmhg.8better outcome. ü
* K/DOKI > Do NOT
exceed 130/80 in renal ptn.
Q.341. How
can glomerular H.T. affect R. function? What is the role of high protein diet?
A. Loss of Nephron mass 8 glomerular hyperfiltration & hypertrophy.
Pre-glomerular
V.D. 8 hyperfiltration due to transmission of systemic B.P. to G.
capill-aries 8 “deranged autoregulation” & renal
damage.
- High
protein intake8 Reduction of preglomerular tone (V.D.)8 G. hyperfiltration & hypertrophy8 renal damage.
Q.342. How can you control glomerular H.T.? C
A. Reduction
of G. pressure (experimental):
reduction in G. cpll. pressure rather than systolic B.P. 8 Protection fr. FSGS.….In
(human)8reduction
of intra-G. hydrostatic pressure8 favorable long term ürenal prognosis.
- Tools : 1. ACE. 2. B.B. 3. Non-pharmacological: FLow
protein diet. Proteinuria in ablation model is closely related to G. H.T. & severity
of proteinuria is closely correlated to G. sclerotic
lesions.
Q.343. In
this view, what is the importance of proteinuria in renal prognosis?
A. Proteinuria is
the F best
predictor of ESRD, not
only in homogenous dis., like Ig A. Dc. Np, M.N.), but also in ch. interstitial nephritis, ch. P.N., V.U. reflux.
Thus once proteinuria occurs 8 it is a major risk f. of progressive
R. function loss, despite many ESRD ptn.s hv no significant
proteinuria.
Q.344. So,
what are the clinical implications of these facts on disease prog-ression?
A. Course of R. dis., correlates well with
antiproteinuric thpy. Actually, Residual proteinuria 8 is a
better “prognostic parameter”
than initial response. It is the driving force for ongoing R. function loss. So,Freduction of proteinuria is pre-requisite
for R. protection له الأولوىة المطلقه >
N.B. Extent of “interstitial
dge” albeit بالرغم من mild 8
i. Worse antiproteiuric response.
ii. Large residual proteinuria.
iii. Worse outcome.
Q.345. In what mechanism, antihyperlipidemics share in renoprotection ?
A. Hyperlipidemia modifies ttt. response, so, it affects prognosis indirectly.
So, Statin improve response to ACEI
in a proteinuria model resistant to thpy. e.g. Pravastatin use for 6
m. reduces proteinuria by ½. G
- Reduction of
the rate of R. function loss by 1.2 ml/min/y.
(slower) é
statin thpy. = Renoprotection.
Interestingly, this fact cannot be
applied to R.Tx. graft. !!!
Q.346. Which
group of anti-H.T. therapy have the 1st priority in renal patient?
A. RAAS blockade
anti-H.T. family is recommended as 1st choice for
those ptn.s.
Q.347. Explain?
A. ACEI ð(see
also, Q. 3).
1) Attenuate R. function loss more
effectively than other groups.
2) Inhibit cleavage of Angio. I. to II.
(the main effector hormone of RAAS).
3) Inhibit breakdown of Bradykinin Ø é Bradykinin
availability.
Q.348.What is the mechanism of renoprotection can this group exert their action?
A. The following mechanisms are
postulated:
1. Hemodynamic : i. Fall in B.P. (systolic).
ii. Fall in intra. “G.B.P”.
thr.: efferent V.D.
2. Reduction of proteinuria (the
main protective mechanism)Ø Ameliorate delet-erious effects
of protein expression on
tub. cells, podocytes & mesangium.
3. RAAS blockadeØ Angio.II. blockade ... as this hormone: Ø
a. Stimulates Growth
F. & inflmm. cytokines Ø
G. & interstitial sclerosis.
b. Induces G. heparanase
Øê
heparin So4 Ø
Loss of G. Permi-selectivity.
(heparin
So4 ü improves permiselectivity). ü
4. Dcr. “bradykinin”
breakdown Øé“bradykinin” availability.
Q.349.What is the role of ACEI in renoprotection in Dc.s ?
A. In Dc.s, ACEI are beneficial in ALL stages of R.
involvement, able to preve-nt or postpone R. involvement. In overt
Np. Ø
they attenuate long-term R. function loss in D.M. I., & attenuate
progression of Incipient Np. (micro.)
to ov-ert albuminuria in normotensive
Dc.s.I., independent effect fr. B.P. control. ACEI are able
to induce regression to normalü in microalbuminuric Dc.s I. All in all, ACEI hv.
remarkable protective effects in reducing long-term R. function loss, owing to their anti-H.T., antiproreinuric
effects. This renoprotection is most apparent inFproteinuric ptn.s.
Q.350. What
about ARBs ?
A. AT1-receptor blockadeØ exerts all anticipated effects of
RAAS blockade such as:
(1) B.P. reduction.
(2) Anti-proteinuric effects.
(3) R.V.D.
é predominant efferent V.D. & other effects.
Q.351. Mention
some Land mark studies in ARBs renoprotection?
* IDNT: Irbesartan
Dc Np trial.
* IRMA: Irbesartan
Reduction in Microalbuminuria in D.M.II.Ø Irb. prevents H.T. ptn. in
D.M. II. convrtion fr. Micro. to overt albuminuria.
* RENAAL: Reduction
in Endpoint in NIDDM with Angio. II. Antagonist Losartan.
AT1-
blockade add sp. R. protective compared to conventional anti -H.T.+ Sp.
Protection as regard rate of R. function
loss & dev. of ESRD & postponing
the need for DX.
Taken together, these studies, in addition to protective
effect of B.P. lowering, add R. protecttive effect by RAAS blockade, wch.
again appear to be linked to anti-proteinuric
effect.
Q.352.What is the role of CCB in renoprotection?
A. Two main
groups are recognized:
i. DHPØ Nifedipine &
Amlodipine.
ii. Non-DHP = Non-proteinuric
CCB Ø verapamil & diltiazem.
T:Nifedipine impair
afferent arterial tone autoregulation (affer. V.D.)Ø transfer Qsystemic to intraglomerular pressure Ø counteract its anti-H.T. protective mch.
(ü): On the otherhand, non-DHP group (verapamil & diltiazem) Ø
Improveü G.B.M.
“permiselectivity” characteristic.
Q.353. Mention some trials concerned with CCB in renoprotection?
MARVAL: Valsartan is
more effective than amlodepine in DM II.
IDNT: Irbisartan 300
mg is more
effective than amlodepine
in reducing risk of ESRD.
BENEDICT: Bergam Nephrologic
Diabetic Complication Trial.
AASK: African American ..: Ramipril
hs better renoprotective ability thn Amlodepine in H.T., nephrosclerotic
blacks.
.. All
in All: Clinical R. protection of CCB appear
to be mainly attributed to their anti-H.T.
effect. J
Q.354. Is there any role for diuretics in the process of renoprotection?
A. Retrospective
studiesØ Rapid
Loss of R. function & lack
of renoprotective effect, Except:
1) Aldosterone blockers (spironolactone)Ø combined R./Cardioprotective
effect.
2) Selective aldosterone blocker (Eblerenon)Ø dcr. B.P. similar to enalapril + Large
reduction in microalbuminuria, wch means effective
monotherapy. ü
Q.355.Antiproteinuric agents have variable benefits & mechanisms, discuss? C
1)
ACEI: Antiproteinuric
effect is attributed to lower systemic & G. tension.
The anti-H.T. is faster, while antiproteinuric
effect is gradual,
sugg. gradual
improvement
in G. permiselectivity,
is contributing antiproteinuric effect as well. Two A
N.B.s:
v In
D.M.: antiproteinuric effect is independent of its hemodynamic (anti-H.T.) action.
v A greater benefit is observed in ptn. é higher basal
proteinuria.
2)
AT1
blockade: they’re parallel to ACEI in :
I.
Reduction
in systemic B.P.
II.
Reduction
in intra-G. pressure. Moreover…,
III.
Restores
G.B.M. “structural integrity”.
IV.
Reduce
“Heparanase” Ø Restore G. “Heparan So4” üexpression Ø improveing B.M. permiselectivity, wch
explain gradual onset of anti-proteinuric action. *** DETAIL study ØDiltiazem Exposed to Telmisartan 80
mg, and Enalapril 20 mg Ø similar rate of R.
function loss & albuminuria.
3)
ACEI/AT1 blocker combination: Additive R.
protective & antiproteinuric (see COOPERATIVE
study).
4)
Renin inhibitors: Aliskiren [Rasilez]150 & 300 mg., Ø êê proteinuria é RAAS blockade.
5)
CCB: Non-DHP Ø ê proteinuria like ACEI
(Non=No
proteinuria), but
according to AASK, IDNT, BENEDICTØ they’re NOT suitable
for long-term R. protection.
6)
Diuretics:
I.
Potentiate
anti-proteinuric action of RAAS blockade.
II.
Aldosterone blockers (Spironolactone) Ø R. protection &
antiproteinuric.
III.
Eblerenone:Ø R. protection
& antiproteinuric independent of anti-H.T. action.
N.B. RAAS
blockade + Spironolactone Ö Risk
of hyperkalemia .
7)
a.
blockers: “Doxazocin”
(Cardura)Øê microalbuminuria in essential
H.T.
8)
Monoxide: Selective
imidazole antagonistØê
proteinuria & G. sclerosis in remnant kidney.
9)
NSAID: (D )
Reduce proteinuria but, êê GFR
due to affer. V.C.
10)
Paracalcitol: see
novel therapy.
11)
Sulo-dexine: see
novel therapy.
Q.356. How much is the extent of SAFETY
of the anti-hyperlipidemic agents?
A. At any level of R.F., HMCo-A drugs are Ø SAFE, even
in adv. R.F., however, V “Fibrates” Ö Dcr. R. function due
to “monocyte toxicity”. D - It’s noteworthy to
mention: antiproteinuric therapy improve
lipid profile.
Q.357.What is the genetic view of renoprotecion?
A. An association is present between Ö “DD” genotype
& progression of R. dis., e.g. {Ig A, Dc Np., APKD, R.Tx. & H.T.
Nephrosclerosis}.
COMMENTS