Q. 376. Who is the 1st physician declares the renal relation to anemia?

 

"Erythropoietin therapy"  

Q. 376. Who is the 1^st physician declares the renal relation to anemia?  

A. Richard Bright, 1836🠞1^st said “After a time the healthy color of the countenance  ملامح الوجه    fades”.

   Richard Bright 1^st to establish Iry clinical Sm of serious kidney disorder known as Bright's disease, or nephritis

Q. 377. Then What?

A. In 1970 & 1980🠞Ischbach &  Adamson 🠞Pioneer work : Epo defined  as 👉responsible of renal anemia.

- In 1985 🠞Isolation of the native Epo. gene, by “Lin & colleague”.

- In 1986🠞r.HuEpo (recombinant human Epo.) colonizing🠞“Chinese hamster” ovary cell.

Q.378. In which site in the kidney Epo. is secreted?

A. Two sites:  ✌

(1) “Peritub.” fibroblast. 👈

(2) “Peritub.” Cpll endothelial cells.👈

Q.379. What are the recent K/DOQI guidelines as regard R. anemia?

* Start Epo thpy at level of 🠞11-13 g/dl.

* Highest threshold 🠞< 13.5 g/dl in adult male.

* Highest threshold 🠞< 11.5 - 12 g/dl in adult female.

Q.380. What is the baseline workup for R. anemia according to recent K/DOQI? 👈

A. Baseline workup for R. anemia 🠊Hemogram: {Erythrocyte indices, Retics , TSAT, S. ferritin, occult blood in stool & either: % hypochromic erythrocytes, or Retics H.B. content}.

Q.381. What are the different forms of Epo ?

A. Epo. forms :

1)   Epo a (Ebrex) & B (Recormon)  (165 a.a.)🠊Glycoprotein produced thr. recombination of the human Epo gene within “Chinese hamster ovary” cells.The B form àmore basic (Sialic a.)🠊 higher in Vivo/Vitro activity. It is larger in volume of distribution, 20 % longer t.½ é i.v. route, delayed more é s.c. route compared to Epoa.

2)   Omega: rHuEpo 🠊produced by baby hamster kidney, é slight hydrophilic ch. ch.

3)   Delta: rHuEpo🠊produced by human cell engineering to translocate the gene.

4)   Pegylated form of erythropoietic stimulating f.🠊Continuous Erythrocyte Receptor Stimulation, FDA approved. Sialc a. & CHO 🠊🠝Duration of action.

5)   Hyperglycosylated(rHuEpo) analogue é 5 N-linked CHO chains(rHuEpo hs 3) designed in 1990 as [Darbepoietin alfa], “Aranesp”(Novel Erythro-poiesis-Stimulating Protein) NESP. Depo & rHuEpo 🠊same mch. & intra-cellular signaling.

Q.382. How can you assist Epo resistance (failure of therapy or poor response)? (see also Q. 396).

A. Resistance to Epo cn be related to the following:

1)   P.H.

2)   Differental WBCs (Infection)           .

3)   Water soluble vitamin deficiency.

4)   Hemolytic status.

5)   Paraproteinemia.

6)   Aliminum intoxication.

7)   High bone turnover.

Q.383 What are the adverse effects of Epo therapy?

A. Adverse effects of Epo therapy:  

1)   Worsening of H.T. (occur accelerated) due to :

                                                                                                     i.   🠝P.R.

                                                                                                    ii.   🠝RBCs mass.

                                                                                                   iii.    Loss of V.D. effect of anemia.

2)   Seizures (not a C.I. for Epo.).

3)   Impaired solute clearance, especially👉K+ 🠞Hyperkalemia & azotemia.

4)   Increased frequency of thrombotic events at, but not confined to, vascular access, esp. é H.B. >13 g/dl.

5)   Icreased. incidence of cancer recuurence.

Q.384. Give the dose & route of Epo?    

A.  Initial dose of darbepoietin a (Dpo)🠊Pre. D.X. 🠞0.45 mcg/kg/w.   &

     Initial dose of (Dpo) for HDX. Ptn.🠊0.75 mcg/kg/w.

     * Dose of rHuEpo 🠊(80-120) u/kg/w.  for s.c. route

                                        (120-180) u/kg/w.  for i.v. route

-      “Europian” recommended 🠊(50-150) u/kg/w. s.c. & i.v.

-      “Canadian” recommended🠊(100-200) u/kg/w. s.c. & i.v.

-      I.P. (intraperitoneal route)🠊Dry abdomen or minimal Dzt.

-      Suggested SAFE rate of correction of anemia 🠊1-2 g/dl/m. ≤ 2-3 g/dl/m. 

-      Slow response to rHuEpo🠊Increased dose by 25-50 % & by 25 % é rapid rise of B.P.

-      Measure H.B. Biweekly at the start then monthly.

-      Iron profile /3 monthly, if erythropoiesis is stable.

Q.385. Why does the B.P. increase é Epo therpy?

A. Two ✌main reasons:

I. Incr. RBCs mass 🠞🠝 P.R.

II. Incr. “vascular reactivity”, due to:   👌

(1)  🠟 N.O. production 🠞Loss of its V.D. effect.

(2)   Release of Endothelin & V.C. protanoids 🠞increased Cytosolic Ca+.

(3)   Trophic effect of Epo on endothelial cell growth.

Q.386.What is the role of oral Iron in ttt. of anemia in H. DX. patient?

A. Pooooor, 😌😌😌 why? :

1. Poor compliance, due to G.I. upset, two cp./d at least, poor education.

2. Poor efficacy, need to be taken é empty stomach, poor absorption.

3. Poor absorption: Po4 binders interfere é iron absorption.

 (Ca acetate 27%- Ca Hco3. 19% - Sevelamer Hcl 10%)

** Oral iron can only be used in:     1. P.D.       2. Pre-DX.  … as much less iron losses.