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Q.337.What is the importance of B.P. control in the renoprotection strategy?



renoprotective meaning renoprotective antihypertensive drugs renoprotective ace inhibitors renoprotective antidiabetic drugs renoprotective agents renoprotective arbs renoprotective antihypertensive renoprotective action telmisartan and renoprotection how to treat chronic kidney disease how to deal with chronic kidney disease renoprotective drugs 


Revise please the abbreviation list on:


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A.Hypertensive Nephrosclerosis” is the 2nd most common cause of ESRD, superseded only by D.M..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 proteinuria8is 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 8deranged 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 betterprognostic 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 Øébradykinin” 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 So4üexpression 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 FibratesÖ 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 ÖDD genotype & progression of R. dis., e.g.  {Ig A, Dc Np., APKD, R.Tx. & H.T. Nephrosclerosis}.