RENOPROTECTION

Q.358. How can life style affect the progression of R. dysfunction?

RENOPROTECTION 

Revise please the abbreviation list on:

https://draft.blogger.com/u/0/blog/post/edit/8610857019469578230/4564412989605988372

Q.358. How can life style affect the progression of Renal dysfunction?

A. Two ✌ major determinants: i. Obesity.   ii. Smoking.

I. Obesity:🠞An association between B.M.I. & ESRD, e.g. FSGS occurs é massive obesity. 

v  Obesity:🠞H.T.-D.M.- insulin resistance-dyslipidemia-as well as a state of “generalized inflammatory state”.       ♨ ♨                                                     

v  Wt. excess:🠞🠝Hyperfiltration & 🠝filtration fraction 🠞 RAAS activity.                  

v  A sp. role of “Leptin” & Adiponectin” is accused.                                                          

v  High sodium intake 🠞🠝risk between BMI & albuminuria.                                             

v  Volume excess 🠞potentiates R. risk of obesity.                                                                

v  Wt. loss 🠞ameliorate R. function abnormalities, also reduction of BMI. by hypocaloric diet 🠞 Reduces proteinuria proportional to Wt. loss.                                   

v  Wt. reduction by “Bariatric surgery” 🠞ameliorate hyperfiltration profile.  

II. Smoking:🠞Incr. the rate of R. function loss, H.T., glucose intolerance .. most prominant in Dc.s  Ø So, smoking abstinence is fundamental.    🚭

Q. 359.What is the effect of risk factors profile?  👍

1)   Clustering of risk f. [H.T.- D.M.- proteinuria- dylipidemia]  hs the foll. impacts: High B.P. Ø aggravates proteinuria.  

2)   Proteinuria🠞hs the pressor effect of sodium retention.   

3)   Proteinuria not only enhances susceptibility to H.T. R. dge, but also enhances lipid-associated R. structural dge.

Q.360. Is there any concordance between cardiac & R. protection?  ۞      

A. The following facts hv been documented:            

R.I.:🠞[H.T., Na retention, Hypervolemia, dyslipidemia, Po4 retention, anemia, hyp-eruricemia & oxidative stress]. On the other hand, H.F., M.I., CMP.🠞 R.I. association.

v  An association betw. “atherosclerotic vasc.” dis & G. sclerosis is present.  

v  “NRP”":🠞incr. risk of “M.I.” 5-6  folds.  

v  Hyperuricemia is us. proportional to severity of proteinuria é esp. atherogenic lipid profile, by elevation of the highly atherogenic Lp(a).        

v  Proteinuria 🠞Endothelial dysfunction.  

v  Proteinuria 🠞Hypoalbuminemia🠞Loss of the protective effect of albumin (It ameliorates the “vascular toxic” effect of oxidized LDL).                 

v  CVS Risk , not only incr. é overt, but also é microalbuminuria in Dc.s & non-DC.s.     

v   Microalbuminuria is a marker of ➳ Generalized “Endothelial dysfunction”. 👍

Q.361.So, what is the feasibility of this dual protection? Mention some trials.

A. It seems that RAAS blockade is the most logical dual-purposeful interven-tion:               * HOPE & micro-HOPE T.🠞Heart Outcome Prevention Evaluation 🠞Reduction of R. & CVS risk by Ramipril 10 mg in ptn. é CVS risk🠞Support this approach.            * RENAAL T.🠞AT1-blockade (Losartan)🠞protects against H.T. & H.F. + Reno-protective.   * LIFE Trial 🠞 Losartan Intervention For Endpoint reduction in H.T.

Q.362. Prescribe a generalized framework for renoprotective measures?   👓

1)   Identify the risk.   

2)   Individualize the risk factor.   

3)   Intervention : pharmacological & non-pharmacological. 

4)   Monitor ttt. efficacy.                

5)   Optimize & adapt therapy.                         

6)   Consider causes of resistance. 

Q.363. Early preventive measures in D.M. is feasible, explain?

A. In type I. D.M.🠞✌ Both strict “glycemic & B.P.” control 

🠞Effective.                         While, Type II. D.M.🠞Only👆achieved by ACE inhibition, in Normo- & H.T. subj..    AT1 block 🠞prevent micro- to overt albuminuria transmission.

Q.364.What about 2ry prevention in R. dis.?

1)   In established R. disease🠞Rigorous B.P. control 🠋130/80 is recommended.            

2)   For proteinuric  ptn.🠞Target B.P.🠋125/75. mmHg.                                                  

3)   ACEI/ARBs🠞1^st line, Except APKD & interstitial nephritis🠞CCB & B.B. cn be 1^st line.                                                                                                       

4)   Dietary “protein” restriction 🠞0.8 g./kg/d. & Na restriction = 50 mEq/d.+ Wt. Loss.

5)   Control of hyperlipidemia.   

6)   Quit Smoking.   🚭

7) 🠋Lpa é HMGCoA & Fibric acid for triglyceridemia.

Q. 365. How to monitor efficacy of therapy?

A. Proteinuria (Albuminuria) ➳ is the best predictor for ttt. efficacy.

Q.366. Then, how to optimize ttt. response?

A. H.T. in renal ptn. is us. Na+-sensitive, So ttt. cn be optimized by:  ✌

       Na+ restriction.

       Saluresis.

Q.367.What harmful effects can Na+ overload exert upon the kidney?

A. Na+ overload:🠞    ✋                       

1)   🠝 B.P.     

2)   Incr. protein “leakage”.   

3)   Renal V.C. &  🠝filtration fraction. 

4)   Crystalluria & Stone formation.               

5)   Glomerular hypertrophy   thr.:

      Hemodynamic effect. &

      Direct growth  promoting f. (non-hemodynamic).

 

Q.368. So, what are the clinical implications of these facts?   

 A. Sodium restriction🠞Enhances the effect of ACEI on B.P., hemodynamics & proteinuria, raises the top of dose response to a large maximum response.  

- A rise of Na+ fr. (50-to 200) mEq.🠞Annihilate (destroy) the antiproteinuric action of ACEI, Almost Completely. كأنّه مَىَّه !!! , Fortunately, the effect of high salt intake cn be completely  overcome  é HZD.

                  { Low salt B.P.= High salt B.P. + HZD }.      👆

     

- Sodium restriction also warranted to augment the antiproteinuric action of the non-DHP group of CCB, Diltiazem.

- A well-known beneficial line of ttt. of crystalluria & stone formation.

Q.369. How could you manage resistance to therapy?   🔒

A. Check up the following items:  🔐

1)   Check compliance.

2)   Dietary:

1.    Sod. restriction = 50 mEq./d. 

2.    Protein restriction.             

3.    Wt. reduction.

3)   Pharmacological: 

i.             Consider dose response in proteinuria.

ii.            Add diuretic.

iii.           More anti-H.T. if B.P. below target.     

iv.           Dual RAAS blockade (ACEI/ARB).    

v.            Consider high dose of RAAS blockade.    

vi.           Add Indomethacin if proteinuria persists.

Q.370. How can combination therapy be beneficial?   ✋

1)   (+) Diuretic 🠞🠋high dietary sod.

2)   (+) Indomethacin🠞🠋proteinuria é no🠋B.P. (X) risk of hyperK+, due to :                i.🠋GFR.    ii. Aldosterone.   iii. Direct effect. …   So, only used é experienced hands + Resin exchange + Low dietary K+.

3)    Dual RAAS blockade (ACEI/ARBs)🠞: H.B. drop, as intense RAAS blockade🠞🠋Epo.

4)   ACEI + (Non-DHP) CCB. in D.M.II. & non-Dc.s

5)   (+) Statin🠞restore anti-proteinuric action of ACEI.

Q.371. Explain The time/course effect in renoprotection?

A. Antiproteinuric agents reach maximum effect in D.M. I. é 1^st week, while in D.M.II., they take several weeks to reach maximum effect.

- On the other hand, the long acting ACEI [Trandalopril] & the renin inhibitor [Remikirin]🠞24 h. B.P. control, but only hv a Diurnal effect.      

Q.372. Mention one trial about combination therapy?

A. “COOPERATIVE” study: Combination thpy of ACEI/ARBs in non-Dc. R. dis.: Trandalopril 3 mg + Losartan 100 mg/d, in non Dc.s🠞more effective thn either thpy monotherapy. Lancet, 2003. 

Q.373. How can “patient factors” affect the response to treatment?

A. The following factors are of noticeable effects :

1)   Race, B.M.I., familial f. 🠞affect RAAS blockade.

2)   Early institution of ttt. before 🠞  interstitial fibrosis ensues .

3)   Renal resp. to ACEI in essential H.T.🠞potentiated é dietary sodium restriction.

4)   Greater response to diuretics, occ. é High risk ptn.

5)   ACE.(I/D), gene & social standard🠞affect resp. to RAAS blockade. 

Q.374.What are the Novel therapeutic modality targets for intervention? 

A. Despite aggressive intervention 🠞 ESRD cannot 😌be preventive, as do CVS complic. of R. dge. However, several Novel 😃approaches are available:

1.    Epo.: As low H.B. predicts R. function loss & its C.V.S. complication, darbe-poietina (Aranesp)reported to reduce CVS. risk in TREAT study: Trial to Reduce CVS Event é Aranesp Therapy, Am Heart J. 2005.

2.    Paricalcitol: باري Use of vit. D. in advanced R.F., to ttt. complication of disturbed Ca/Po4 balance. A recently developed vit. D compound, Parical-citol, for hyperparathyroidism

🠞 Antiproteinuric & Renoprotective effect. * Antiproteinuric effect of oral Paricalcitol (Zemplar) in CKD, Kid int, 2005.

3.    Sulodexine صولو & HeparanSo4: Loss of GAG & Heparan So4 🠞[Distor-ted G.B.M. integrity & loss of anionic sites + changes in extracellular matrix] 🠞Proteinuria & Loss of renal function. … So,

 - Hparan & other GAG🠞Reduces proteinuria + preserve G.B.M. “integrity”. Oral ttt. é GAG (Sulodexine)🠞Reduces micro/ macroalb. in Dc.s

Q.375. Summarize the broad lines of renoprotection?    ❋❋

A. “Conclusion”:       

The endpoint in R. protection🠞🠋B.P.,🠋proteinuria, thr. RAAS blockade in Dc.s & non-Dc.s (1^st choice), as EARLY as possible. High dose RAAS blockade, Dual RAAS blockade, Dietary measures, Aldosterone blockers, Statin, Epo., GAG, …. Should be considered.